Diisopropylethylamine → tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetate

HRID 2202215Notes

Reaction equation

HRID 2202215 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:27]=[C:28]([NH:37][C:38]([C@H:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH3:51])=[CH:47][CH:48]=3)[CH2:43][CH2:42][NH:41]2)=[O:39])[CH:29]=[C:30]([F:36])[C:31]=1[Si:32]([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.[C:61]([O:65][C:66](=[O:75])[CH:67]=[C:68]1[CH2:71][CH:70]([C:72](O)=[O:73])[CH2:69]1)([CH3:64])([CH3:63])[CH3:62]>CN(C=O)C.O>[F:25][C:26]1[CH:27]=[C:28]([NH:37][C:38]([C@H:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH3:51])=[CH:47][CH:48]=3)[CH2:43][CH2:42][N:41]2[C:72]([CH:70]2[CH2:69][C:68](=[CH:67][C:66]([O:65][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:75])[CH2:71]2)=[O:73])=[O:39])[CH:29]=[C:30]([F:36])[C:31]=1[Si:32]([CH3:33])([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59834904Cyclobutanecarboxylic acid, 3-[2-(1,1-dimethylethoxy)-2-oxoethylidene]-HCID 131735726(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide

Product 1

HCID 131735728tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetateYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (148 mg, 0.39 mmol) was added to a solution of (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide (138 mg, 0.35 mmol), DIEA (0.068 mL, 0.39 mmol) and 3-(2-(tert-butoxy)-2-oxoethylidene)cyclobutanecarboxylic acid (83 mg, 0.39 mmol) in DMF (4 mL), and the mixture was stirred at room temperature for 2.5 hr. To the reaction mixture was added water to give pale-yellow precipitates. The precipitate was collected by filtration to give tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetate (138 mg, 0.236 mmol, 67%).

Workup

  1. customto give pale-yellow precipitates
  2. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-c7a00f0b0b0d4b7793759e19aabae055
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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