Dimethylformamide → HCID 71143938, compound

HRID 2370800Notes

Reaction equation

HRID 2370800 reaction equation
Br[C:2]1[C:3]([C@H:8]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[NH:9][C:10]([C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[CH:17][CH:18]=[N:19]3)=[CH:14][CH:13]=2)=[O:11])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:32][N:33](C=O)C.CCOC(C)=O>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:32]([C:2]1[C:3]([C@H:8]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=2)[NH:9][C:10]([C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[CH:17][CH:18]=[N:19]3)=[CH:14][CH:13]=2)=[O:11])=[N:4][CH:5]=[CH:6][CH:7]=1)#[N:33]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 71144135HCID 71144135, compound

Product 1

HCID 71143938HCID 71143938, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

To a microwave vial were added (S)—N-((3-bromopyridin-2-yl)(4-(trifluoromethyl)phenyl)methyl)quinoline-7-carboxamide (Example 195) (0.100 g, 0.206 mmol), zinc cyanide (0.026 mL, 0.411 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.024 g, 0.021 mmol), and DMF (1.3 mL). The resulting mixture was then subjected to microwave irradiation at 130° C. for 30 min. EtOAc (10 mL) and H2O (10 mL) were then added, and the resulting mixture was stirred at rt for 5 min. The organic layer was collected, dried over MgSO4 and concentrated. The residue was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired product, which was dissolved in MeOH (1 mL). The solution was washed through PL_HCO3 MP-SPE resin and the resin was washed with MeOH (2×1 mL). The combined filtrates were concentrated and dried in vacuo to give the title compound as a yellow solid. 1H NMR (400 MHz, MeOH) δ ppm 8.98 (dd, J=4.1, 1.6 Hz, 1H), 8.93 (dd, J=4.9, 1.6 Hz, 1H), 8.60 (s, 1H), 8.46 (d, J=8.4 Hz, 1H), 8.25 (dd, J=7.8, 1.6 Hz, 1H), 8.08 (s, 2H), 7.70-7.81 (m, 4H), 7.66 (dd, J=8.4, 4.3 Hz, 1H), 7.58 (dd, J=7.8, 4.9 Hz, 1H), 6.91 (s, 1H). MS (ESI pos. ion) m/z: 433.1 (M+H).

Workup

  1. customirradiation at 130° C. for 30 min
  2. customThe organic layer was collected
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-513f5b368a654973818560eead6f6cd8
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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