Diisopropylethylamine → HCID 118308207, compound

HRID 1750690Notes

Reaction equation

HRID 1750690 reaction equation
Cl.[NH2:2][CH:3]1[CH2:7][C:6]([F:9])([F:8])[CH2:5][CH:4]1[NH:10][C:11](=[O:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[N:22]=[CH:21][CH:20]=[N:19]1.Cl[C:25]1[N:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:8][C:6]1([F:9])[CH2:5][CH:4]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:18]2[N:19]=[CH:20][CH:21]=[N:22]2)[CH:3]([NH:2][C:25]2[N:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=2)[CH2:7]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 133170192-Chloro-5-(trifluoromethyl)pyrimidineHCID 118025227HCID 118025227, compound2×

Product 1

HCID 118308207HCID 118308207, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of N-(2-amino-4,4-difluorocyclopentyl)-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 42; 120 mg, 0.39 mmol) in dry DMSO (1.2 ml) was added 2-chloro-5-(trifluoromethyl)pyrimidine (CAS number 69034-12-4; 70 mg, 0.384 mmol) and DIPEA (183 μl, 1.047 mmol). The reaction mixture was heated in a sealed vial at 140° C. for 17 hours then partitioned between ethyl acetate and water. The organics were washed with water, filtered through a hydrophobic frit and concentrated in vacuo. The crude material was purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol) then was chirally separated using SFC (Waters prep30/MS system using 20% Isopropanol, Daicel AD 10 mm id×250 mm long columns at 30 ml/min, 40° C. and 100 bar) to afford the title compound as a single enantiomer.

Workup

  1. customthen partitioned between ethyl acetate and water
  2. washThe organics were washed with water
  3. filtrationfiltered through a hydrophobic frit
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol)
  6. customthen was chirally separated
  7. customSFC (Waters prep30/MS system using 20% Isopropanol, Daicel AD 10 mm id×250 mm long columns at 30 ml/min, 40° C. and 100 bar)

Sources & evidence

ORD record
ord-f32b5a0422d34d79859352856bc0cf14
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

Loading…