1,2-Dichloroethane → Hydrochloric Acid

HRID 888401Notes

Reaction equation

HRID 888401 reaction equation
[OH:1][C:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][N:15]=2)[CH:13]=1)[C:8]([OH:10])=O)([CH3:4])[CH3:3].[F:21][C:22]([F:33])([F:32])[C:23]1[N:28]=[CH:27][C:26]([C@H:29]([NH2:31])[CH3:30])=[CH:25][N:24]=1.C(Cl)C[Cl:36].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.FC(F)(F)C(O)=O>CN(C)C=O.O>[ClH:36].[OH:1][C:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][N:15]=2)[CH:13]=1)[C:8]([NH:31][C@@H:29]([C:26]1[CH:25]=[N:24][C:23]([C:22]([F:33])([F:32])[F:21])=[N:28][CH:27]=1)[CH3:30])=[O:10])([CH3:3])[CH3:4]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 66661534(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamineHCID 685016863-(1-Hydroxy-1-methylethyl)-5-(5-methylpyridin-2-yl)benzoic acid

Product 2

HCID 313Hydrochloric AcidHCID 426029983-(1-Hydroxy-1-methylethyl)-5-(5-methylpyridin-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of the hydrochloride salt of 3-(1-hydroxy-1-methylethyl)-5-(5-methylpyridin-2-yl)benzoic acid (165 mg, 0.536 mmol) in N,N-dimethylformamide (2.1 mL) was added the hydrochloride salt of (1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamine (170 mg, 0.643 mmol), EDC (123 mg, 0.643 mmol), HOBT (82.0 mg, 0.536 mmol) and triethylamine (0.374 mL, 2.68 mmol) and the mixture was heated to 60° C. After 1 h the mixture was allowed to cool to ambient temperature, water and trifluoroacetic acid were added. The mixture was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→50% water/acetonitrile with 0.1% trifluoroacetic acid). Treatment with 2 M hydrochloric acid in diethyl ether gave the title compound as a hydrochloride salt (179 mg). HRMS 445.1845 (M+1). 1H NMR (500 MHz, CD3OD): δ 9.04 (s, 2H); 8.69 (s, 1H); 8.46 (d, J=8.4 Hz, 1H); 8.28-8.21 (m, 4H); 5.37 (q, J=7.2 Hz, 1H); 2.60 (s, 3H); 1.73 (d, J=7.2 Hz, 3H); 1.64 (s, 6H).

Workup

  1. temperatureto cool to ambient temperature
  2. customThe mixture was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→50% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-ec861279958e420cb1bc39812ef555b2
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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