Diisopropylethylamine → HCID 90040593, compound

HRID 1485890Notes

Reaction equation

HRID 1485890 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[NH:16][C:17]([C@@H:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][NH:20]1)=[O:18].[C:29]([O:33][C:34]([NH:36][C@@H:37]([CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)[C:38](O)=[O:39])=[O:35])([CH3:32])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:29]([O:33][C:34](=[O:35])[NH:36][C@@H:37]([CH:41]1[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]1)[C:38]([N:20]1[CH2:21][CH2:22][C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:19]1[C:17](=[O:18])[NH:16][C:10]1[C:11]([F:15])=[CH:12][CH:13]=[CH:14][C:9]=1[F:8])=[O:39])([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131736761HCID 131736761, compound

Product 1

HCID 90040593HCID 90040593, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid (2,6-difluoro-phenyl)-amide trifluoroacetate (52 mg, 129 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonylamino)-2-cyclohexylacetic acid (33.3 mg, 129 μmol, Eq: 1.00) and HATU (54.1 mg, 142 μmol, Eq: 1.1) in DMF (300 μL) at 0° C. was added DIEA (50.1 mg, 67.7 μL, 388 μmol, Eq: 3). The reaction was stirred at RT for 1 h diluted with water and extracted with EtOAc. The combined organics were washed with water, brine, dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography to give {(S)-1-cyclohexyl-2-[(S)-1-(2,6-difluoro-phenylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester (62 mg) as a white foam.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organics were washed with water, brine
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-cd3fedfee75846e0a350dbc46d6f8afa
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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