Diisopropylethylamine → HCID 90040531, compound

HRID 1485898Notes

Reaction equation

HRID 1485898 reaction equation
F[C:2](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][N:20]1[C:29](=[O:35])[C@@H:30]([NH2:34])[CH:31]([CH3:33])[CH3:32])=[O:18].[C:36]([O:40][C:41]([NH:43][C@@H:44]([CH3:48])[C:45]([OH:47])=O)=[O:42])([CH3:39])([CH3:38])[CH3:37].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:36]([O:40][C:41](=[O:42])[N:43]([C@H:44]([C:45](=[O:47])[NH:34][C@H:30]([C:29]([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:35])[CH:31]([CH3:33])[CH3:32])[CH3:48])[CH3:2])([CH3:37])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131736765HCID 131736765, compound

Product 1

HCID 90040531HCID 90040531, compoundYield 65.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-((S)-2-amino-3-methyl-butyryl)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid (2-chloro-6-fluoro-phenyl)-amide trifluoroacetate (48 mg, 92.7 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonylamino)propanoic acid (17.5 mg, 92.7 μmol, Eq: 1.00), HATU (38.8 mg, 102 μmol, Eq: 1.1) in DMF (300 μL) at 0° C. was added DIEA (35.9 mg, 48.6 μL, 278 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-[(S)-1-(2-chloro-6-fluoro-phenylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-methyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester (36 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-b74228f7d7de4f879e2f8fcd46423f0a
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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