Dimethylformamide → HCID 123485213, compound

HRID 1509231Notes

Reaction equation

HRID 1509231 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[NH:22][C:23](=O)NC[C:26]=4[N:27]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].CI.[CH3:40][N:41]([CH:43]=[O:44])[CH3:42]>>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:40]4[N:41]([CH3:42])[C:43](=[O:44])[N:22]([CH3:23])[CH2:21][C:26]=4[N:27]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 123632245HCID 123632245, compound

Product 1

HCID 123485213HCID 123485213, compoundYield 61%

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-7-phenyl-1,2,3,4-tetrahydropyrido[3,2-d]pyrimidin-6-yl)phenyl)cyclobutyl)carbamate (46 mg, 0.10 mmol) in dry DMF (1 ml) at −78 C was added sodium hydride (3.9 mg, 0.10 mmol) and methyliodide (6.1 μl, 0.10 mmol) under nitrogen. The bath was removed and the resulting mixture was stirred for 1 h at room temperature. The mixture was cooled down to −78 C. Sodium hydride (3.9 mg, 0.10 mmol) and methyliodide (6.10, μl, 0.10 mmol) were added under nitrogen. The bath was removed and the resulting mixture was stirred for 1 h at room temperature. Water was added and the mixture was extracted with EtOAc (3×10 ml). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 50% EtOAc in cyclohexane) to give the title compound (30 mg, 61%). 1H NMR (500 MHz, CDCl3): 7.20-7.19 (7H, m), 7.13-7.11 (2H, m), 7.02 (1H, s), 5.00 (1H, br s), 4.56 (2H, s), 3.27 (3H, s), 3.03 (3H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.79-1.65 (1H, m), 1.40-1.10 (9H, br)

Workup

  1. customThe bath was removed
  2. temperatureThe mixture was cooled down to −78 C
  3. customThe bath was removed
  4. stirringthe resulting mixture was stirred for 1 h at room temperature
  5. additionWater was added
  6. extractionthe mixture was extracted with EtOAc (3×10 ml)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-90eb18c58bb74975857df1612183df4d
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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