Diisopropylethylamine → HCID 11720828, compound

HRID 907610Notes

Reaction equation

HRID 907610 reaction equation
[CH:1]1([CH2:4][S:5]([CH2:8][C@H:9]([NH:13][C@@H:14]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:15]([F:25])([F:24])[O:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:10](O)=[O:11])(=[O:7])=[O:6])[CH2:3][CH2:2]1.Cl.[NH2:34][C:35]1([C:38]#[N:39])[CH2:37][CH2:36]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:38]([C:35]1([NH:34][C:10](=[O:11])[C@@H:9]([NH:13][C@@H:14]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:15]([F:25])([F:24])[O:16][C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)[CH2:8][S:5]([CH2:4][CH:1]2[CH2:2][CH2:3]2)(=[O:6])=[O:7])[CH2:37][CH2:36]1)#[N:39]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 67391530HCID 67391530, compound

Product 1

HCID 11720828HCID 11720828, compoundYield 39.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 3-cyclopropylmethanesulfonyl-2(R)-[2,2-difluoro-2-(4-fluoro-phenoxy)-1(S)-(4-fluorophenyl)ethylamino]propionic acid (0.2 g, 0.42 mmol) and 1-aminocyclopropanecarbonitrile hydrochloride (0.060 g, 0.5 mmol) in DMF (3 ml), HATU (0.16 g, 0.42 mmol) and diisopropylethylamine (0.183 ml, 1 mmol) was added. After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate and washed with water, sat. NaHCO3 and brine. After drying over sodium sulfate, the solvent was evaporated and the residue was purified by flash chromatography, using ethyl acetate/hexanes (1/1) as eluent to give the title compound as a white solid (0.09 g, 39%). 1HNMR (DMSO-d6): δ 9.01 (1H, s), 7.47 (2H, m), 7.21 (2H, m), 7.13 (2H, m), 4.29 (1H, q), 3.74 (1H, m), 3.4 (2H, m), 3.19 (3H, m), 1.36 (2H, m), 1.10 (1H, m), 1.00 (1H, m), 0.72 (1H, m), 0.57 (2H, m), 0.30 (2H, m). LC/MS, M+1: 540.3; M−1: 538.3.

Workup

  1. additionwas added
  2. washwashed with water, sat. NaHCO3 and brine
  3. dry with materialAfter drying over sodium sulfate
  4. customthe solvent was evaporated
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-852ecfd8f8ce4f4bab826ee3e7141feb
Source dataset
uspto-grants-2011_09
Patent number
US08013186B2

Reaction notes

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