Dimethylformamide → HCID 58468260, compound

HRID 2094643Notes

Reaction equation

HRID 2094643 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:29]2[C:38]3[C:33](=[C:34](Br)[CH:35]=[C:36]([CH3:39])[CH:37]=3)[CH:32]=[CH:31][CH:30]=2)[C@@H:9]([C:13]2[CH:28]=[CH:27][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.[CH3:41][N:42](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:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:29]2[C:38]3[C:33](=[C:34]([C:41]#[N:42])[CH:35]=[C:36]([CH3:39])[CH:37]=3)[CH:32]=[CH:31][CH:30]=2)[C@@H:9]([C:13]2[CH:28]=[CH:27][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58468276HCID 58468276, compound

Product 1

HCID 58468260HCID 58468260, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a solution of ethyl N-(4-{(1S)-1-[(4-chlorophenyl)(5-bromo-7-methyl-1-naphthyl)methyl]butyl}benzoyl)-β-alaninate (40 mg, 0.064 mmol) in DMF (3 mL) was added zinc cyanide (8.3 mg, 0.071 mmol) and Pd(Ph3P)4 (22.3 mg, 0.019 mmol). The resulting reaction mixture was stirred at 110° C. for 24 hours, then concentrated. The resulting residue was purified by preparative TLC eluting with 40% EtOAc/hexanes afforded a 9:1 mixture of naphthyl regioisomers. The residue was purified by preparative HPLC (Chiralcel OD column) eluting with 5% EtOH/heptane to afford the major diastereomer of the title compound. 1H NMR (500 MHz, CDCl3): δ 8.14 (s, 1H); 7.90 (d, J=8.5 Hz, 1H); 7.65 (d, J=7.5 Hz, 1H); 7.63 (s, 1H); 7.48 (d, J=8.5 Hz, 2H); 7.42 (m, 1H); 7.36 (d, J=8.5 Hz, 2H); 7.26 (d, J=8.0 Hz, 2H); 7.20 (d, J=8.5 Hz, 2H); 6.66 (m, 1H); 5.00 (d, J=11.5 Hz, 1H); 4.13 (q, J=7.2 Hz, 2H); 3.62 (q, J=11.8 Hz, 2H); 3.56 (m, 1H); 2.54 (q, 14.5 Hz, 2H); 2.54 (s, 3H); 1.62-1.51 (m, 2H); 1.25 (t, J=7.3 Hz, 3H), 1.06-1.00 (m, 2H); 0.74 (t, J=7.2 Hz, 3H). LC3 4.06 min. [M+H]+ 567.

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated
  3. customThe resulting residue was purified by preparative TLC
  4. washeluting with 40% EtOAc/hexanes
  5. customafforded
  6. additiona 9:1 mixture of naphthyl regioisomers
  7. customThe residue was purified by preparative HPLC (Chiralcel OD column)
  8. washeluting with 5% EtOH/heptane

Sources & evidence

ORD record
ord-15c0400639144414b59638ae274313bd
Source dataset
uspto-grants-2013_05
Patent number
US08445538B2

Reaction notes

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