Methylamine hydrochloride → (+)-N4-(2,6-dimethoxypyridin-3-yl)-N2-[2,3-dihydro-2-(N-methylamino)carbonylbenzofuran-5-yl]-5-fluoro-2,4-pyrimidinediamine

HRID 1960917Notes

Reaction equation

HRID 1960917 reaction equation
Cl.[CH3:2][NH2:3].[CH3:4][O:5][C:6]1[C:11]([NH:12][C:13]2[C:18]([F:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]4[O:28][CH:27]([C:29]([O:31]C)=O)[CH2:26][C:25]=4[CH:33]=3)[N:14]=2)=[CH:10][CH:9]=[C:8]([O:34][CH3:35])[N:7]=1>>[CH3:4][O:5][C:6]1[C:11]([NH:12][C:13]2[C:18]([F:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]4[O:28][CH:27]([C:29]([NH:3][CH3:2])=[O:31])[CH2:26][C:25]=4[CH:33]=3)[N:14]=2)=[CH:10][CH:9]=[C:8]([O:34][CH3:35])[N:7]=1

Participants

3

Reactant 2

HCID 6364545Methylamine hydrochlorideHCID 22060286N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-N4-(2,6-dimethoxypyridin-3-yl)-5-fluoro-2,4-pyrimidinediamine

Product 1

HCID 22060644(+)-N4-(2,6-dimethoxypyridin-3-yl)-N2-[2,3-dihydro-2-(N-methylamino)carbonylbenzofuran-5-yl]-5-fluoro-2,4-pyrimidinediamine

Procedure

In like manner to the preparation of (±)-N4-(3,4-difluorophenyl)-5-fluoro-N2-[2-(N-methylamino)carbonyl-2,3-dihydrobenzofuran-5-yl]-2,4-pyrimidinediamine, the reaction of methyl amine Hydrogen Chloride with (±)-N4-(2,6-dimethoxypyridin-3-yl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine gave (±)-N4-(2,6-dimethoxypyridin-3-yl)-N2-[2,3-dihydro-2-(N-methylamino)carbonylbenzofuran-5-yl]-5-fluoro-2,4-pyrimidinediamine. 1H NMR (CD3OD): δ 7.98 (d, 1H, J=8.1 Hz), 7.81 (d, 1H, J=3.6 Hz), 7.39 (bd, 1H, J=2.4 Hz), 7.06 (dd, 1H, J=2.4 and 8.7 Hz), 6.72 (d, 1H, J=8.1 Hz), 6.31 (d, 1H, J=8.7 Hz), 5.07 (dd, 1H, J=6.3 Hz), 3.96 (s, 3H), 3.93 (s, 3H), 3.46 (dd, 1H, J=7.8 and 10.5 Hz), 3.19 (dd, 1H, J=5.7 and 6.3 Hz), 2.77 (d, 3H, J=4.8 Hz); LCMS: purity: 98%; MS (m/e): 441 (MH+).

Workup

  1. customIn like manner to the preparation of (±)-N4-(3,4-difluorophenyl)-5-fluoro-N2-[2-(N-methylamino)carbonyl-2,3-dihydrobenzofuran-5-yl]-2,4-pyrimidinediamine

Sources & evidence

ORD record
ord-f29cf29e55234f868c08590de880584e
Source dataset
uspto-grants-2013_04
Patent number
US08410266B2

Reaction notes

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