Dimethylformamide → HCID 86683644, compound

HRID 1509263Notes

Reaction equation

HRID 1509263 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:28])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].C(=O)([O-])[O-].[K+].[K+].[CH3:42]I.C(=O)(O)[O-].[Na+].C[N:50]([CH:52]=O)C>>[CH3:42][CH:52]1[NH:50][C:26]2[N:27]=[C:18]([C:15]3[CH:14]=[CH:13][C:12]([C:8]4([NH:7][C:6](=[O:35])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[CH2:9][CH2:10][CH2:11]4)=[CH:17][CH:16]=3)[C:19]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[CH:20][C:21]=2[NH:22][C:23]1=[O:28]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 6328Methyl iodide3×HCID 11430Potassium Carbonate3×HCID 516892Sodium BicarbonateHCID 123632245HCID 123632245, compound

Product 1

HCID 86683644HCID 86683644, compoundYield 42%

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 (71 mg, 0.15 mmol) in dry DMF (1 ml) was added potassium carbonate (21 mg, 0.15 mmol) and methyl iodide (9.4 μl, 0.15 mmol) under nitrogen. The resulting mixture was stirred overnight at room temperature. Potassium carbonate (42 mg, 0.30 mmol) and methyl iodide (18.8 μl, 0.30 mmol) were added under nitrogen. The resulting mixture was stirred for 1 hr at room temperature. Potassium carbonate (146 mg, 1.05 mmol) and methyl iodide (66 μl, 1.05 mmol) were added under nitrogen. The resulting mixture was stirred for 4 hr at 60° C. Saturated sodium bicarbonate solution was added and the mixture was extracted with ethyl acetate (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 100% EtOAc in cyclohexane) to give the title compound (31 mg, 42%). LCMS (Method D): RT=1.437 min, M+H+=485. 1H NMR (500 MHz, CDCl3): 7.25-7.38 (7H, m), 7.20-7.25 (2H, m), 7.16 (1H, s), 5.47 (1H, br s), 5.10 (1H, br s), 4.73 (2H, s), 3.35 (3H, s), 2.25-2.70 (4H, br m), 2.00-2.13 (1H, m), 1.75-1.85 (1H, m), 1.10-1.40 (9H, br).

Workup

  1. stirringThe resulting mixture was stirred for 1 hr at room temperature
  2. stirringThe resulting mixture was stirred for 4 hr at 60° C
  3. extractionthe mixture was extracted with ethyl acetate (3×10 ml)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-afcd3496feb64090bd5128a29fa31223
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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