N-methyl-2-pyrrolidone → 8-Cyano-10-(2-cyclopropylethyl)-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one

HRID 456982Notes

Reaction equation

HRID 456982 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[C:12](=[O:16])[NH:13][CH:14]=[N:15][C:6]=3[C:5]([CH2:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)([C:17]([F:20])([F:19])[F:18])[C:4]=2[CH:3]=1.[CH3:26][N:27]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2].[Zn]>[C:26]([C:2]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[C:12](=[O:16])[NH:13][CH:14]=[N:15][C:6]=3[C:5]([CH2:21][CH2:22][CH:23]3[CH2:24][CH2:25]3)([C:17]([F:18])([F:20])[F:19])[C:4]=2[CH:3]=1)#[N:27]

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 1354160158-Chloro-10-(2-cyclopropylethyl)-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one

Product 1

HCID 1358136218-Cyano-10-(2-cyclopropylethyl)-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-oneYield 46%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalyst

Conditions

Temperature
170 °C

Procedure

A mixture of 17 (110 mg, 0.297 mmol), Zn(CN)2 (71 mg, 0.594 mmol, 2 equiv), [(t-Bu)3P]2 Pd (0.78 g, 0.149 mmol, 0.5 equiv) and Zn powder (29 mg, 0.446 mmol, 1.5 eq) were suspended in anhydrous NMP and degassed. The reaction mixture was heated to 170° C. for 30 h. After cooling to 25° C., the reaction was quenched with 2 N NH4OH (20 mL) and extracted with EtOAc (2×25 mL). The combined organic phases were washed with brine, dried (MgSO4) and concentrated. Chromatography (SiO2, 50 to 60% EtOAc-hexane) afforded the desired product as an off-white solid (49 mg, 46%). mp>280° C. ESI HRMS m/z 361.1293 (M++H, C18H16F3N4O requires 361.1276).

Workup

  1. customdegassed
  2. temperatureAfter cooling to 25° C.
  3. customthe reaction was quenched with 2 N NH4OH (20 mL)
  4. extractionextracted with EtOAc (2×25 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5c1206dc29ea41278d0366795670dbdc
Source dataset
uspto-grants-2007_03
Patent number
US07186830B2

Reaction notes

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