1-Hydroxybenzotriazole → N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-3,5-difluoro-pyridine-2-carboxamide

HRID 77589

Reaction equation

HRID 77589 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[F:33][C:34]1[C:35]([C:41](O)=[O:42])=[N:36][CH:37]=[C:38]([F:40])[CH:39]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl>[C:25]([NH:24][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][N:15]([C:17]3[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=3)[CH2:16][C@:8]2([C:4]2[CH:3]=[C:2]([NH:1][C:41]([C:35]3[C:34]([F:33])=[CH:39][C:38]([F:40])=[CH:37][N:36]=3)=[O:42])[CH:7]=[CH:6][CH:5]=2)[N:9]=1)(=[O:32])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27832623,5-Difluoropyridine-2-carboxylic acidHCID 86762768N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 86762777N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-3,5-difluoro-pyridine-2-carboxamideYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (0.30 g, 0.67 mmol) is dissolved in dichloromethane (10 mL) and 3,5-difluoropyridine-2-carboxylic acid (138 mg, 0.87 mmol), 1-hydroxybenzotriazole (185 mg, 1.34 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (169 mg, 0.87 mmol) are added. Diisopropylethylamine (0.35 mL, 2 mmol) is added and the reaction is stirred at room temperature overnight. The reaction is purified directly with silica gel chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to give the title compound (330 mg, 84%). ES/MS (m/e): 590 (M+H).

Workup

  1. customThe reaction is purified directly with silica gel chromatography
  2. washeluting with a 0-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-eba7504c48f44cb9bf2e4a7eaf3e24cd
Source dataset
uspto-grants-2014_09
Patent number
US08841293B1

Linked notes

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