Dimethylformamide → HCID 58560979, compound

HRID 2408157Notes

Reaction equation

HRID 2408157 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([C:36]([F:39])([F:38])[F:37])[C:34]=1[Cl:35])[O:5][C@@H:6]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C@@H:7]([C:11]1[CH:24]=[CH:23][C:14]([C:15]([NH:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[O:16])=[CH:13][CH:12]=1)[CH2:8][CH2:9][CH3:10].[CH3:40][N:41](C=O)C>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.[C-]#N.[Zn+2].[C-]#N>[Cl:35][C:34]1[C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:4]([O:5][C@@H:6]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[C@@H:7]([C:11]2[CH:24]=[CH:23][C:14]([C:15]([NH:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[O:16])=[CH:13][CH:12]=2)[CH2:8][CH2:9][CH3:10])=[CH:3][C:2]=1[C:40]#[N:41]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58560992HCID 58560992, compound

Product 1

HCID 58560979HCID 58560979, compound

Reagents, catalysts & solvents 2

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

Procedure

The product from Step B (200 mg, 0.309 mmol), (Ph3P)4Pd (107 mg, 0.093 mmol), and zinc cyanide (54.4 mg, 0.473 mmol) were stirred in DMF (3 mL) at 120° C. for 24 hours. After cooling to RT, the mixture was filtered through celite, then the filtrate was concentrated. The resulting residue was purified by reverse phase HPLC eluting with 60-100% acetonitrile/water+0.1% TFA. Following lyophilization, this afforded the title compound. 1H NMR (500 MHz, (CD3)2CO): δ 7.78 (d, J=8.5 Hz, 2H); 7.62 (d, J=3.0 Hz, 1H); 7.56 (d, 2.5 Hz, 1H); 7.41 (d, J=3.0 Hz, 2H); 7.39 (d, J=2.5 Hz, 2H); 7.34 (d, J=8.5 Hz, 2H); 5.90 (d, J=7.0 Hz, 1H); 3.61 (m, 2H); 3.29 (m, 1H); 2.63 (m, 2H); 2.62-1.77 (m, 1H); 1.62-1.55 (m, 1H); 1.15-1.08 (m, 2H); 0.76 (t, J=7.2 Hz, 3H); LC3 4.09 min. (M+H)+ 593.

Workup

  1. filtrationthe mixture was filtered through celite
  2. concentrationthe filtrate was concentrated
  3. customThe resulting residue was purified by reverse phase HPLC
  4. washeluting with 60-100% acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-1fa3f86a9ec447c3b273bc41f3020a73
Source dataset
uspto-grants-2014_08
Patent number
US08809579B2

Reaction notes

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