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Crystalline forms of intermediates of 6-(3-Chloro-2-fluorobenzyl)-1-[1(S)- (hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

IP.com Disclosure Number: IPCOM000234659D
Publication Date: 2014-Jan-27

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The IP.com Prior Art Database

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CRYSTALLINE FORMS OF INTERMEDIATES IN THE SYNTHESIS OF N-[4-[(3- CHLORO-4-FLUOROPHENYL) AMINO]-7-[[(3S)-TETRAHYDRO-3-FURANYL]

OXY]-6-QUINAZOLINYL]-4(DIMETHYLAMINO)-2-BUTENAMIDE

    For the purpose of clarity and as an aid in the understanding of the intermediates involved in the synthesis of N-[4-[(3-Chloro-4-fluorophenyl) amino]-7-[[(3S)-tetrahydro-3- furanyl] oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide, as disclosed herein, the following terms and abbreviations are defined below:
Compound A-5 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

Compound A-7 (S)-N-(3-chloro-4-fluorophenyl)-6-nitro-7-(tetrahydrofuran-3- yloxy)quinazolin-4-amine


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Compound A-8 (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3- yloxy)quinazoline-4,6-diamine.

Compound A-12 (S)-diethyl-2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3- yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate

Compound A-14 2-(dimethylamino)-1-hydroxyethanesulfonic acid


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Crystalline Form of Compound A-5

    The crystalline form of Compound A-5 is characterized by an X-ray powder diffraction pattern having peaks at 7.1, 7.6, 12.8, 13.4, 17.7, 20.8, 21.4, 26.3 and 28.4 degrees two theta ± 0.2 degrees two theta; and/or an X-ray powder diffraction pattern as depicted in Figure 1; and/or an FTIR spectrum as depicted in Figure 2.

Intensity (counts)

4000

3000

2000

1000

0

5

10

15

20

25

30

35

2Theta (°)

Figure 1. PXRD pattern of crystalline Form of Compound A-5

Figure 2. FTIR spectrum of crystalline Form of Compound A-5



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Crystalline Form of Compound A-7

    The crystalline form of Compound A-7 is characterized by an X-ray powder diffraction pattern having peaks at 7.3, 10.1, 11.4, 11.8, 16.1, 16.7, 20.9 and 25.9 degrees two theta ± 0.2 degrees two theta; and/or an X-ray powder diffraction pattern as depicted in Figure 3; and/or and/or an FTIR spectrum as depicted in Figure 4.

Intensity (counts)

30000

20000

10000

0

5

10

15

20

25

30

35

2Theta (°)

Figure 3. PXRD pattern of crystalline form of Compound A-7

Figure 4. FTIR spectrum of crystalline form of Compound A-7


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Crystalline Form I of Compound A-8

    The crystalline form I of Compound A-8 is characterized by an X-ray powder diffraction pattern having peaks at 8.5, 12.4, 13.1, 16.4, 19.1, 20.4, 21.0 and 25.8degrees two theta ± 0.2 degrees two theta; and/or an X-ray powder diffraction pattern as depicted in Figure 5; and/or an FTIR spectrum as depicted in Figure 6.

Intensity (counts)

4000

3000

2000

1000

0

5

10

15

20

25

30

35

2Theta (°)

Figure 5. PXRD pattern of crystalline form I of Compound A-8.

Figure 6. FTIR spectrum of crystalline form I of Compound A-8.


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Crystalline Form II of Compound A-8

    The crystalline form II of Compound A-8 is characterized by an X-ray powder diffraction pattern having peaks at 8.9, 10.6, 11.5, 14.5, 18.8, 22.6 and 26.1 degrees two theta ± 0.2 degrees two theta; and/or an X-ray powder diffraction pattern as depicted in Figure 7;...