N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide → 5-amino-N-(5-((4S,5R)-4-amino-5-fluoroazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxamide

HRID 1915905Notes

Reaction equation

HRID 1915905 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([CH3:22])[C:6]=1[N:7]1[CH2:13][CH2:12][CH:11]([F:14])[CH:10]([NH:15]C(=O)C(F)(F)F)[CH2:9][CH2:8]1.C(OC([NH:30][C:31]1[S:35][C:34]([C:36]2[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=2[F:43])=[N:33][C:32]=1[C:44](O)=[O:45])=O)(C)(C)C>>[NH2:30][C:31]1[S:35][C:34]([C:36]2[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=2[F:43])=[N:33][C:32]=1[C:44]([NH:1][C:2]1[CH:3]=[N:4][N:5]([CH3:22])[C:6]=1[N:7]1[CH2:13][CH2:12][C@@H:11]([F:14])[C@@H:10]([NH2:15])[CH2:9][CH2:8]1)=[O:45]

Participants

3

Reactant 2

HCID 86680076N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamideHCID 866801125-((Tert-butoxycarbonyl)amino)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxylic acid

Product 1

HCID 749831745-amino-N-(5-((4S,5R)-4-amino-5-fluoroazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxamide

Procedure

Following the procedure for Example 221 starting from N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide and 5-(tert-butoxycarbonyl-amino)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxylic acid gave, after purification via silica gel column chromatography (5% MeOH/DCM with 1% 7 N ammonia in MeOH), 294 as a cream solid (107 mg, 48%). 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 7.90-7.84 (m, 1H), 7.82 (s, 1H), 7.17-7.11 (m, 1H), 7.04 (dd, J=11.1, 8.4 Hz, 1H), 6.10 (s, 2H), 4.95-4.78 (m, 1H), 3.74 (s, 3H), 3.49-3.33 (m, 3H), 3.24-3.11 (m, 2H), 2.40 (s, 3H), 2.40-2.26 (m, 1H), 2.09-1.91 (m, 2H), 1.87-1.77 (m, 1H). Alkyl NH2 not seen. LCMS (ES+) m/z 462 (M+1)

Workup

  1. customgave
  2. customafter purification via silica gel column chromatography (5% MeOH/DCM with 1% 7 N ammonia in MeOH), 294 as a cream solid (107 mg, 48%)

Sources & evidence

ORD record
ord-363ca18ba6964cc2b233295e2bd798df
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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