1,2-Dichloroethane → HCID 86603236, compound

HRID 1272387Notes

Reaction equation

HRID 1272387 reaction equation
[CH3:1][C:2]([CH3:23])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([OH:12])=O)=[O:6])[CH3:3].Cl.[CH2:25]([CH:32]1[C:37]2[N:38]=[C:39]([C:42]([F:45])([F:44])[F:43])[N:40]=[CH:41][C:36]=2[CH2:35][CH2:34][NH:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(Cl)CCl.CN1CCOCC1>C(#N)C>[CH3:23][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([N:33]1[CH2:34][CH2:35][C:36]2[CH:41]=[N:40][C:39]([C:42]([F:45])([F:43])[F:44])=[N:38][C:37]=2[CH:32]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:12])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidHCID 131726348HCID 131726348, compound

Product 1

HCID 86603236HCID 86603236, compoundYield 115.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 133 mg (0.40 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid and 162 mg (0.50 mmol) of 8-benzyl-2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine, hydrochloride in 1.5 mL of acetonitrile at 0° C. was treated sequentially with 81 mg (0.42 mmol) of EDC and 0.047 mL (0.42 mmol) of N-methyl morpholine. After 10 min, the mixture was warmed to ambient temperature and stirred for 3 h, then partitioned between 10 mL of ethyl acetate and 4 mL of water. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried and concentrated to give 281 mg of the title compound as a mixture of diastereomers. Purification by flash chromatography (silica gel, 10 to 35% ethyl acetate/hexane) followed by HPLC on a Chiralpak AD column (9% ethanol/hexane) gave 51 mg of the faster eluting isomer and 47 mg of the slower eluting isomer.

Workup

  1. custompartitioned between 10 mL of ethyl acetate and 4 mL of water
  2. washThe organic layer was washed sequentially with saturated aqueous sodium bicarbonate solution and brine
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ac6b75a3447d42ca9bc9bd7f96e26743
Source dataset
uspto-grants-2007_04
Patent number
US07208498B2

Reaction notes

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