Diisopropylethylamine → HCID 16041338, compound

HRID 2076944Notes

Reaction equation

HRID 2076944 reaction equation
C(N(C(C)C)CC)(C)C.[F:10][C:11]1([F:40])[CH2:16][C@@H:15]([C:17](O)=[O:18])[C@H:14]([C:20]2[C:24]([C:25]3[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=3)=[CH:23][N:22]([CH2:35][C:36]([F:39])([F:38])[F:37])[N:21]=2)[CH2:13][CH2:12]1.Cl.[NH2:42][C:43]1([C:46]#[N:47])[CH2:45][CH2:44]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:46]([C:43]1([NH:42][C:17]([C@@H:15]2[CH2:16][C:11]([F:10])([F:40])[CH2:12][CH2:13][C@H:14]2[C:20]2[C:24]([C:25]3[CH:26]=[CH:27][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:29][CH:30]=3)=[CH:23][N:22]([CH2:35][C:36]([F:39])([F:37])[F:38])[N:21]=2)=[O:18])[CH2:45][CH2:44]1)#[N:47]

Participants

6

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 25131532HCID 25131532, compound

Product 1

HCID 16041338HCID 16041338, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (3.2 mL, 18 mmol) was added in one portion to a solution of (1R,2R)-5,5-difluoro-2-[4-[4-(methylsulfonyl)phenyl]-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl]cyclohexanecarboxylic acid (1.69 g, 3.63 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (1.16 g, 9.83 mmol) and HATU (1.72 g, 4.53 mmol) in DMF (10 mL) with stirring at rt for 2.5 h. The reaction vessel contents were then partitioned between ethyl acetate and water and the layers were separated. The aqueous phase was extracted with additional ethyl acetate and the combined organics were washed with 2 M HCl, 10% Na2CO3 and saturated NaCl aqueous solutions, followed by drying over Na2SO4. Concentration in vacuo and flash chromatography on silica gel eluting with 22.5/77.5 acetone/benzene provided the title compound as a colorless powder upon trituration with a mixture of hexanes and ether. 1H NMR (400 MHz, acetone d6) δ 8.03 (1H, s), 7.99 (2H, d, J= 8.5 Hz), 7.83 (1H, overlapped m), 7.81 (2H, d, J= 8.5 Hz), 5.05 (2H, q, J= 8.8 Hz), 3.36 (1H, m), 3.18 (3H, s), 3.12 (1H, m), 2.23 (1H, m), 2.15-1.95 (4H, m), 1.79 (1H, m), 1.37 (2H, m), 1.05 (1H, m), 0.81 (1H, m). MS: (+ESI) 531.0 [M+H]+.

Workup

  1. customThe reaction vessel contents were then partitioned between ethyl acetate and water
  2. customthe layers were separated
  3. extractionThe aqueous phase was extracted with additional ethyl acetate
  4. washthe combined organics were washed with 2 M HCl, 10% Na2CO3 and saturated NaCl aqueous solutions
  5. dry with materialby drying over Na2SO4
  6. concentrationConcentration in vacuo and flash chromatography on silica gel eluting with 22.5/77.5 acetone/benzene

Sources & evidence

ORD record
ord-0f396acc71e045fba2ca98c8babce1d8
Source dataset
uspto-grants-2011_04
Patent number
US07928091B2

Reaction notes

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