Dimethylformamide → tert-Butyl((1R)-4-(2-(6-isoquinolinylcarbonyl)hydrazino)-4-oxo-1-(4-(trifluoromethyl)benzyl)butyl)carbamate

HRID 598901Notes

Reaction equation

HRID 598901 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.CN(C(O[N:22]1[N:30]=NC2C=CC=N[C:23]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:38]([O:42][C:43](=[O:61])[NH:44][C@@H:45]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:53][CH:52]=1)[CH2:46][CH2:47]NN)([CH3:41])([CH3:40])[CH3:39].CN(C=[O:66])C>>[C:38]([O:42][C:43](=[O:61])[NH:44][C@@H:45]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]([F:59])([F:58])[F:60])=[CH:53][CH:52]=1)[CH2:46][CH2:47][C:23]([NH:22][NH:30][C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[CH:1]=[N:2][CH:3]=[CH:4]2)=[O:13])=[O:66])([CH3:40])([CH3:39])[CH3:41]

Participants

5

Reactant 4

HCID 6228Dimethylformamide3×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22128831Isoquinoline-6-carboxylic acidHCID 57950716tert-butyl((1S)-3-hydrazino-1-(4-(trifluoromethyl)benzyl)propyl)carbamate

Product 1

HCID 57950611tert-Butyl((1R)-4-(2-(6-isoquinolinylcarbonyl)hydrazino)-4-oxo-1-(4-(trifluoromethyl)benzyl)butyl)carbamateYield 71%

Procedure

Isoquinoline-6-carboxylic acid (0.22 g, 1.3 mmol) (commercially available from AstaTech Product List (Order Number 62874)) and HATU (0.50 g, 1.3 mmol) were mixed in 10 mL DMF along with 0.21 mL DEA. The mixture was stirred at room temperature for 15 minutes. The mixture was added dropwise to a DMF solution of tert-butyl((1S)-3-hydrazino-1-(4-(trifluoromethyl)benzyl)propyl)carbamate (0.45 g, 1.2 mmol) and 0.21 mL of DEA in 10 mL DMF. The resulting mixture was stirred at room temperature for 1 hour. After the solvent was removed, the residue was dissolved in EtOAc and saturated aqueous sodium bicarbonate, and dried over sodium sulfate. The solvent was evaporated and the residue was triturated with DCM to provide the product as an off-white solid (0.45 g, 71%). LCMS (API-ES) m/z: 531 (M+H+).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 hour
  2. customAfter the solvent was removed
  3. dissolutionthe residue was dissolved in EtOAc
  4. dry with materialsaturated aqueous sodium bicarbonate, and dried over sodium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was triturated with DCM

Sources & evidence

ORD record
ord-0c1106f0bd6a4efa812ad90310ec4466
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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