Diisopropylethylamine → N-[1-[(4,4-Difluorocyclohexyl)methyl]-2-(1,1-difluoroethyl)-1H-benzimidazol-5-yl]acetamide

HRID 1987213Notes

Reaction equation

HRID 1987213 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:21])[CH3:20])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:55][C:56]([F:61])([CH3:60])[C:57](O)=O>CN(C=O)C>[F:16][C:13]1([F:17])[CH2:14][CH2:15][CH:10]([CH2:9][N:8]2[C:7]3[CH:6]=[CH:5][C:4]([NH:18][C:19](=[O:21])[CH3:20])=[CH:3][C:2]=3[N:1]=[C:57]2[C:56]([F:61])([F:55])[CH3:60])[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57441085N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide

Product 1

HCID 57441087N-[1-[(4,4-Difluorocyclohexyl)methyl]-2-(1,1-difluoroethyl)-1H-benzimidazol-5-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide (99 mg, 0.333 mmol), DIPEA (0.087 mL, 0.500 mmol), HATU (140 mg, 0.366 mmol) and 2,2-difluoropropionic acid (40 mg, 0.366 mmol) were stirred in 5 mL of DMF at rt for 1 h. The solvent was evaporated. The residue was dissolved in 3 mL of glacial AcOH and heated at 80° C. for 2 h. The solvent was evaporated. The product was dissolved in EtOAc and washed with aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by silica gel flash chromatography using EtOAc as eluent. Yield: 100 mg (81%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.39-1.52 (m, 2 H), 1.57-1.63 (m, 1 H), 1.64-1.71 (m, 3 H), 2.06-2.16 (m, 3 H), 2.22 (s, 3 H), 2.29 (m, 3 H), 4.25 (d, J=7.42 Hz, 2 H), 7.31 (s, 1 H), 7.35 (d, J=8.79 Hz, 1 H), 7.60 (dd, J=8.89, 1.86 Hz, 1 H), 7.86 (d, J=1.76 Hz, 1 H).

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in 3 mL of glacial AcOH
  3. customThe solvent was evaporated
  4. dissolutionThe product was dissolved in EtOAc
  5. washwashed with aqueous NaHCO3 solution, saturated aqueous NaCl solution
  6. dry with materialdried over anhydrous Na2SO4
  7. customThe product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-0f5982dc054d4c908933b16e86edc543
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

Loading…