Diisopropylethylamine → HCID 90040598, compound

HRID 1485892Notes

Reaction equation

HRID 1485892 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][N:20]1[C:29](=[O:38])[C@@H:30]([NH2:37])[CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)=[O:18].[C:39]([O:43][C:44]([N:46]([CH3:52])[C@@H:47]([CH3:51])[C:48](O)=[O:49])=[O:45])([CH3:42])([CH3:41])[CH3:40].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:39]([O:43][C:44](=[O:45])[N:46]([C@H:47]([C:48](=[O:49])[NH:37][C@@H:30]([CH:31]1[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]1)[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[F:8])=[O:38])[CH3:51])[CH3:52])([CH3:40])([CH3:41])[CH3:42]

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 131736762HCID 131736762, compound

Product 1

HCID 90040598HCID 90040598, compoundYield 80.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-((S)-2-amino-2-cyclohexyl-acetyl)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid (2,6-difluoro-phenyl)-amide trifluoroacetate (63.6 mg, 117 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid (22.2 mg, 117 μmol, Eq: 1.00), HATU (49.1 mg, 129 μmol, Eq: 1.1) in DMF (500 μL) at 0° C. was added DIEA (45.5 mg, 61.5 μL, 352 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-cyclohexyl-2-[(S)-1-(2,6-difluoro-phenylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxo-ethylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester (58 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-92f02587184149e6a48413d4c776c618
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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