2-Aminophenol → HCID 178520042, compound

HRID 1816843Notes

Reaction equation

HRID 1816843 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([OH:14])=O)=[CH:9][CH:10]=2)[NH:5][N:4]=1)=[O:2].N[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[OH:22].C[N:24](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O>[OH:22][C:17]1[CH:18]=[CH:19][C:20]([NH:24][C:12]([C:8]2[CH:7]=[C:6]3[C:11]([C:3]([CH:1]=[O:2])=[N:4][NH:5]3)=[CH:10][CH:9]=2)=[O:14])=[CH:21][CH:16]=1

Participants

6

Reactant 4

HCID 58012-AminophenolHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178520043HCID 178520043, compound

Product 1

HCID 178520042HCID 178520042, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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.

Workup

  1. customThe starting material was prepared
  2. customThe solvent was removed by vacuum
  3. customthe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-f2e43349d2ba451db568893c3ebf48fe
Source dataset
uspto-grants-2005_04
Patent number
US06884890B2

Reaction notes

Loading…