1,2-Dichloroethane → HCID 90041912, compound

HRID 530375Notes

Reaction equation

HRID 530375 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([OH:27])=O)[CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.Cl.[CH3:29][O:30][C:31](=[O:34])[CH2:32][NH2:33].C(Cl)CCl.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)C.C(OCC)(=O)C.Cl.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([NH:33][CH2:32][C:31]([O:30][CH3:29])=[O:34])=[O:27])[CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:18])[F:17])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

12

Reactant 5

HCID 111,2-DichloroethaneHCID 8471Triethylamine2×HCID 757711-HydroxybenzotriazoleHCID 122755Glycine methyl ester hydrochloride2×HCID 73297228HCID 73297228, compound

Product 1

HCID 90041912HCID 90041912, compound

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3′-methyl-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-carboxylic acid (80 mg, 0.178 mmol), glycine methyl ester hydrochloride (24.6 mg, 0.196 mmol), DMAP (2.2 mg, 0.018 mmol), EDC (47.7 mg, 0.249 mmol), and triethylamine (0.074 mL, 0.534 mmol) in DMF (4 mL) was stirred for 15 hours at ambient temperature and then heated to 60° C. for 90 minutes. The reaction mixture was cooled to ambient temperature and then charged with HOBT (12.0 mg, 0.078 mmol), glycine methyl ester hydrochloride (24.6 mg, 0.196 mmol), and triethylamine (0.074 mL, 0.534 mmol). The reaction mixture was heated to 60° C. for 5 hours, cooled to ambient temperature, and diluted with diethyl ether (10 mL), ethyl acetate (10 mL), aqueous hydrochloric acid (1 M, 10 mL), and water (5 mL). The layers were separated, and the organic layer was washed with aqueous hydrochloric acid (1 M, 10 mL), aqueous sodium hydroxide (2×10 mL), saturated aqueous sodium bicarbonate (10 mL), and brine (10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give methyl N-[(3′-methyl-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-yl)carbonyl]glycinate which was used without further purification. MS ESI calc'd. for C22H20F3N4O3 [M+H]+ 445, found 445.

Workup

  1. temperatureheated to 60° C. for 90 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. temperatureThe reaction mixture was heated to 60° C. for 5 hours
  4. temperaturecooled to ambient temperature
  5. customThe layers were separated
  6. washthe organic layer was washed with aqueous hydrochloric acid (1 M, 10 mL), aqueous sodium hydroxide (2×10 mL), saturated aqueous sodium bicarbonate (10 mL), and brine (10 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c4b3e36c46c14b80a712045a97b262e0
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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