Dimethylformamide → HCID 67003511, compound

HRID 2199700Notes

Reaction equation

HRID 2199700 reaction equation
Br[C:2]1[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=3)[C@@H:12]([C:16]3[CH:31]=[CH:30][C:19]([C:20]([NH:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([Cl:39])[CH:3]=1.[CH3:40][N:41](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:39][C:4]1[CH:3]=[C:2]([C:40]#[N:41])[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=3)[C@@H:12]([C:16]3[CH:31]=[CH:30][C:19]([C:20]([NH:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58513008HCID 58513008, compound

Product 1

HCID 67003511HCID 67003511, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A degassed mixture of ethyl N-(4-{(1S)-1-[(7-bromo-5-chloro-1-benzothien-3-yl)(4-chlorophenyl)methyl]butyl}benzoyl)-β-alaninate (0.128 g, 0.198 mmol), zinc cyanide (0.046 g, 0.40 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.114 g, 0.099 mmol) in anhydrous DMF (2.9 mL) was heated at 80° C. for 2.5 hours. After cooling to room temperature, the solution was concentrated, then the residue was purified by silica gel chromatography eluting with 35% EtOAc/hexanes. The resulting material was further purified by preparative HPLC (Daicel AD-H chiral column, 2 cm×25 cm, 16% IPA/Heptane, 20 mL/min) to provide the title compound as a white solid. LC1: 4.12 min. (M+H)+ 593.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe solution was concentrated
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with 35% EtOAc/hexanes
  5. customThe resulting material was further purified by preparative HPLC (Daicel AD-H chiral column, 2 cm×25 cm, 16% IPA/Heptane, 20 mL/min)

Sources & evidence

ORD record
ord-1a18ae2aada34c53a572591ccf6b1af5
Source dataset
uspto-grants-2016_06
Patent number
US09359339B2

Reaction notes

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