Diisopropylethylamine → HCID 118252502, compound

HRID 1485884Notes

Reaction equation

HRID 1485884 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]([C@@H:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][NH:13]1)=[O:11].[C:21]([O:25][C:26]([NH:28][C@@H:29]([CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)[C:30](O)=[O:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].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:21]([O:25][C:26](=[O:27])[NH:28][C@@H:29]([CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1)[C:30]([N:13]1[CH2:14][C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:12]1[C:10](=[O:11])[NH:9][C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])=[O:31])([CH3:24])([CH3:22])[CH3:23]

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 131736758HCID 131736758, compound

Product 1

HCID 118252502HCID 118252502, compoundYield 82.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2,3-dihydro-1H-isoindole-1-carboxylic acid (2,6-difluoro-phenyl)-amide (160 mg, 412 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonylamino)-2-cyclohexylacetic acid (106 mg, 412 μmol, Eq: 1.00) and HATU (172 mg, 453 μmol, Eq: 1.1) in DMF (500 μL) at 0° C. was added DIEA (160 mg, 216 μL, 1.24 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-cyclohexyl-2-[(S)-1-(2,6-difluoro-phenyl-carbamoyl)-1,3-dihydro-isoindol-2-yl]-2-oxo-ethyl}-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-aec712656b184f1e84e5f738b9eae0a9
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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