Diisopropylethylamine → HCID 118252521, compound

HRID 1485886Notes

Reaction equation

HRID 1485886 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:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][N:20]1[C:28](=[O:37])[C@@H:29]([NH2:36])[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[O:18].[C:38]([O:42][C:43]([N:45]([CH3:51])[C@@H:46]([CH3:50])[C:47](O)=[O:48])=[O:44])([CH3:41])([CH3:40])[CH3:39].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:38]([O:42][C:43](=[O:44])[N:45]([C@H:46]([C:47](=[O:48])[NH:36][C@@H:29]([CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)[C:28]([N:20]1[CH2:21][C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=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:37])[CH3:50])[CH3:51])([CH3:39])([CH3:40])[CH3:41]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131736759HCID 131736759, compound

Product 1

HCID 118252521HCID 118252521, compoundYield 85.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-((S)-2-amino-2-cyclohexyl-acetyl)-2,3-dihydro-1H-isoindole-1-carboxylic acid (2,6-difluoro-phenyl)-amide trifluoroacetate (179 mg, 339 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid (64.2 mg, 339 μmol, Eq: 1.00), HATU (142 mg, 373 μmol, Eq: 1.1) in DMF (1 mL) at 0° C. was added DIEA (132 mg, 178 μL, 1.02 mmol, 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-cyclohexyl-2-[(S)-1-(2,6-difluoro-phenylcarbamoyl)-1,3-dihydro-isoindol-2-yl]-2-oxo-ethylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester (174 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-81c9d2ba1a7d4b1da1481cbfd45a2773
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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