Hydrazinecarboxylic acid, ethyl ester → (S)-tert-butyl 3-((8-fluoro-3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)isoquinolin-1-yl)amino)pyrrolidine-1-carboxylate

HRID 1476878Notes

Reaction equation

HRID 1476878 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([NH:14][C@H:15]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]2)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][C:7]=2[F:13])#[N:2].[NH:27]([C:29]([O:31]CC)=O)N.[N:34]1CCCCN2CCCCC=12.[H-].[Na+]>>[F:13][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[C:5]([NH:14][C@H:15]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]1)=[N:4][C:3]([C:1]1[NH:27][C:29](=[O:31])[NH:34][N:2]=1)=[CH:12]2

Participants

5

Reactant 4

HCID 20064Hydrazinecarboxylic acid, ethyl esterHCID 24758Sodium hydrideHCID 129337972,3,4,5,7,8,9,10-Octahydropyrido[1,2-a][1,3]diazepineHCID 90387010(S)-tert-butyl 3-((3-cyano-8-fluoroisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate

Product 1

HCID 136597077(S)-tert-butyl 3-((8-fluoro-3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)isoquinolin-1-yl)amino)pyrrolidine-1-carboxylateYield 25.8%

Conditions

Temperature
170 °C

Procedure

To a mixture of (S)-tert-butyl 3-((3-cyano-8-fluoroisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate (1.0 g, 2.81 mmol), ethyl hydrazinecarboxylate (7.74 g, 74.40 mmol) and 2,3,4,5,7,8,9,10-octahydropyrido[1,2-a][1,3]diazepine (1.13 g, 7.44 mmol) was added a catalytic amount of NaH (10 mg, 0.25 mmol). The reaction mixture was heated to 170° C. for 30 minutes. The crude product was purified by preparative HPLC to give the title compound as pale yellow solid (300 mg, 25.7%). ESI-MS m/z [M+H]+ 415.2.

Workup

  1. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-0b0b4a4eafc241229e924ed3430968f6
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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