1,2-Diamino-4,5-difluorobenzene → HCID 135839327, compound

HRID 1816842Notes

Reaction equation

N1C2C=CC=CC=2N=C1C1C2C(=CC(C(O)=O)=CC=2)NN=1.[OH:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:32]2[CH:40]=[C:39]3[C:35]([C:36]([CH:41]=O)=[N:37][NH:38]3)=[CH:34][CH:33]=2)=[O:31])=[CH:25][CH:24]=1.[F:43][C:44]1[C:49]([F:50])=[CH:48][C:47]([NH2:51])=[C:46]([NH2:52])[CH:45]=1>>[F:43][C:44]1[C:49]([F:50])=[CH:48][C:47]2[NH:51][C:41]([C:36]3[C:35]4[C:39](=[CH:40][C:32]([C:30]([NH:29][C:26]5[CH:25]=[CH:24][C:23]([OH:22])=[CH:28][CH:27]=5)=[O:31])=[CH:33][CH:34]=4)[NH:38][N:37]=3)=[N:52][C:46]=2[CH:45]=1

Participants

Reactant 3

HCID 27367551,2-Diamino-4,5-difluorobenzene

HCID 135839310319474-36-7

HCID 178520042HCID 178520042, compound

Product 1

HCID 135839327HCID 135839327, compound

Procedure

Using the same procedure as for the synthesis of 3-(1H-benzoimidazol-2-yl)-1H-indazole-6-carboxylic acid in Example 53(a), step (ii), N-(4-hydroxyphenyl)-3-formyl-1H-indazole-6-carboxamide and 4,5-difluoro 1,2-phenylenediamine gave 3-(5,6-difluoro-1H-benzoimidazol-2-yl)-N-(4-hydroxyphenyl)1H-indazole-6-carboxamide as a tan solid. 1H NMR (DMSO-d6) δ 13.99 (1H, s), 13.27 (1H, s), 10.21 (1H, s), 9.25 (1H, s), 8.52 (1H, d, J=8.7 Hz), 8.21 (1H, s), 7.85 (1H, d, J=9.0 Hz), 7.80 (1H, t, J=9.8 Hz), 7.55 (2H, d, J=8.7 Hz), 7.47 (1H, t, J=9.8 Hz), 6.75 (2H, d, J=8.7 Hz). MS (APCI positive) 406. The starting material was prepared as follows: To a solution of 3-formyl-1H-indazole-6-carboxylic acid (1.6 g, 8.4 mmol) and 4 aminophenol (1.8 g, 16.8 mmol) in dry dimethylformamide (35 mL) was added HATU (3.8 g, 16.8 mmol) followed by triethylamine (1.4 mL, 10.1 mmol). The reaction was stirred at room and monitored by TLC and LC/MS. After two hours the reaction was complete. The solvent was removed by vacuum and the product was purified by flash column chromatography using ethyl acetate: petroleum ether 1:1 to pure ethyl acetate. N-(4-Hydroxyphenyl)-3-formyl-1H-indazole-6-carboxamide was isolated as a tan colored solid. 1H NMR (DMSO-d6) δ 6.79 (2H, d, 8.9 Hz), 759 (2H, d, 8.9 Hz), 7.94 (1H, d, 9.8 Hz), 8.24 (1H, d, 8.2 Hz), 8.31 (1H, s), 9.31 (1H, br s), 10.27 (2H, s). MS (APCI pos) 282.1.

Sources & evidence

ORD record: ord-145331bd55884259811e9c145d808355
Source dataset: uspto-grants-2005_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06884890B2

Reaction notes

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