Diisopropylethylamine → HCID 178494936, compound

HRID 2202321Notes

Reaction equation

HRID 2202321 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:26][C:27]1[CH:28]=[C:29]([NH:40][C:41]([C@H:43]2[C:52]3[C:47](=[CH:48][C:49]([O:53][CH3:54])=[CH:50][CH:51]=3)[CH2:46][CH2:45][NH:44]2)=[O:42])[CH:30]=[C:31]([F:39])[C:32]=1[C:33]([CH3:38])([CH3:37])[CH2:34][O:35][CH3:36].[C:55]([O:59][C:60](=[O:69])[CH2:61][C@@H:62]1[CH2:65][C@H:64]([C:66](O)=[O:67])[CH2:63]1)([CH3:58])([CH3:57])[CH3:56].CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:26][C:27]1[CH:28]=[C:29]([NH:40][C:41]([C@H:43]2[C:52]3[C:47](=[CH:48][C:49]([O:53][CH3:54])=[CH:50][CH:51]=3)[CH2:46][CH2:45][N:44]2[C:66]([C@@H:64]2[CH2:63][C@H:62]([CH2:61][C:60]([O:59][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:69])[CH2:65]2)=[O:67])=[O:42])[CH:30]=[C:31]([F:39])[C:32]=1[C:33]([CH3:37])([CH3:38])[CH2:34][O:35][CH3:36]

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 118622780HCID 118622780, compoundHCID 178451083HCID 178451083, compound

Product 1

HCID 178494936HCID 178494936, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (114 mg, 0.30 mmol) was added to a solution of (R)—N-(3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochloride (120 mg, 0.27 mmol), cis-3-(2-(tert-butoxy)-2-oxoethyl)cyclobutanecarboxylic acid (61.2 mg, 0.29 mmol) and DIEA (0.107 mL, 0.60 mmol) in DMF (2 mL) at room temperature, and the mixture was stirred overnight at room temperature. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane) to give tert-butyl 2-(cis-3-((R)-1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate (120 mg, 0.200 mmol, 73.4%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9efc784f8e014e7bb26108e3e4e2016e
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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