Diisopropylethylamine → HCID 90040703, compound

HRID 1485896Notes

Reaction equation

HRID 1485896 reaction equation
FC(F)(F)C(O)=O.[Cl: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]([CH3:43])[CH3:42])[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]([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[Cl:8])=[O:39])[CH:41]([CH3:42])[CH3:43])([CH3:30])([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131736764HCID 131736764, compound

Product 1

HCID 90040703HCID 90040703, compoundYield 48.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid (2-chloro-6-fluoro-phenyl)-amide trifluoroacetate (80 mg, 191 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (41.5 mg, 191 μmol, Eq: 1.00) and HATU (79.9 mg, 210 μmol, Eq: 1.1) in DMF (500 μL) at 0° C. was added DIEA (74.1 mg, 100 μL, 573 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-[(S)-1-(2-chloro-6-fluoro-phenylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-methyl-propyl}-carbamic acid tert-butyl ester (47 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-1a75cc98e13644f3b92b81d4ef140dbc
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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