Dimethyl Sulfate → HCID 178495570, compound

HRID 656623Notes

Reaction equation

HRID 656623 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:38])[C:5]2=[C:6]([CH2:8][C@H:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[N:31]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH:14]([CH2:20][CH2:21][OH:22])[C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[N:7]=1.[H-].[Na+].S(OC)(O[CH3:45])(=O)=O>C1COCC1>[NH2:1][C:2]1[N:3]=[C:4]([CH3:38])[C:5]2=[C:6]([CH2:8][C@H:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[N:31]=3)[NH:10]/[C:11]/2=[N:12]\[O:13][CH:14]([CH2:20][CH2:21][O:22][CH3:45])[C:15]([N:17]([CH3:18])[CH3:19])=[O:16])[N:7]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 178489729HCID 178489729, compound

Product 1

HCID 178495570HCID 178495570, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-((Z)—((R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-4-hydroxy-N,N-dimethylbutanamide (0.03 mmol, 16 mg) in THF (2 mL) was added 50% NaH (0.034 mmol, 1.65 mg) at 0° C. under N2 atmosphere. The reaction mixture was stirred for 15 minutes and dimethyl sulphate (4.08 μL, 0.043 mmol) was added. The reaction mixture was stirred at r.t. for 3 h. Quenched with MeOH (1 mL) and purified by LCMS to afford the title compound 2-((Z)—((R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-4-methoxy-N,N-dimethylbutanamide (95, 3.6 mg, 25%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.81-2.06 (m, 2H) 2.47 (s, 3H) 2.70-2.80 (m, 1H) 2.83 (d, J=10.61 Hz, 3H) 3.05 (d, J=7.58 Hz, 3H) 3.07-3.17 (m, 1H) 3.20 (d, J=4.80 Hz, 3H) 3.31-3.39 (m, 2H) 3.40-3.49 (m, 2H) 3.87 (d, J=3.79 Hz, 3H) 4.80-4.93 (m, 1H) 5.06-5.22 (m, 1H) 6.83-6.90 (m, 1H) 7.20 (d, J=8.84 Hz, 1H) 7.23-7.32 (m, 2H) 7.44 (ddd, J=14.34, 8.91, 5.81 Hz, 1H) 7.85 (td, J=7.83, 3.28 Hz, 1H). MS (ES) [M+H] calculated for C27H33FN7O4, 538.58. found 538.40.

Workup

  1. stirringThe reaction mixture was stirred at r.t. for 3 h
  2. customQuenched with MeOH (1 mL)
  3. custompurified by LCMS

Sources & evidence

ORD record
ord-f18de8b6d00947e6ae9faa009a6123a4
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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