Methylamine → 4-[2-(5-Chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ylamino]-N-methyl nicotinamide
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[C:23]([C:24]([OH:26])=O)=[CH:22][N:21]=[CH:20][CH:19]=3)[C:11]3[O:16][CH2:15][CH2:14][C:12]=3[N:13]=2)[CH:7]=1.[CH2:28]([N:30](CC)CC)C.CN.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[C:23]([C:24]([NH:30][CH3:28])=[O:26])=[CH:22][N:21]=[CH:20][CH:19]=3)[C:11]3[O:16][CH2:15][CH2:14][C:12]=3[N:13]=2)[CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 4-[2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ylamino]-nicotinic acid (75 mg, 0.19 mmol, 1 eq) in DMF (2 ml) was added triethylamine (30 μl, 0.21 mmol, 1.1 eq) followed by methylamine (1.17 ml, 3.89 mmol, 2 M solution in THF, 20 eq). To the suspension was added a solution of PyBrOP (100 mg, 0.21 mmol, 1.2 eq) in DMF (1 ml) dropwise. The reaction mixture was stirred at room temperature for 16 h. The reaction was concentrated in vacuo and the residue was triturated with ether (2×20 ml). The crude residue was purified by flash column chromatography (5% MeOH in CHCl3) to afford 4-[2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ylamino]-N-methyl nicotinamide, i.e. compound of formula (44) (20 mg, 26%) as a white solid.
Workup
- concentrationThe reaction was concentrated in vacuo
- customthe residue was triturated with ether (2×20 ml)
- customThe crude residue was purified by flash column chromatography (5% MeOH in CHCl3)
Sources & evidence
- ORD record
- ord-092e87e3ea504870ae123475ad125569
- Source dataset
- uspto-grants-2011_07
- Patent number
- US07977342B2
Reaction notes
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