2-chloro-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine → (+/-)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

HRID 1753596Notes

Reaction equation

HRID 1753596 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([C:10]([O:12][CH3:13])=[O:11])[CH2:7][C:6]=2[CH:14]=1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[CH:28]=[C:27]3[O:29][CH2:30][O:31][C:24]=2[C:25]([F:33])=[C:26]3[F:32])[C:19]([F:34])=[CH:18][N:17]=1>>[CH3:13][O:12][C:10]([CH:8]1[CH2:7][C:6]2[CH:14]=[C:2]([NH:1][C:16]3[N:21]=[C:20]([NH:22][C:23]4[CH:28]=[C:27]5[O:29][CH2:30][O:31][C:24]=4[C:25]([F:33])=[C:26]5[F:32])[C:19]([F:34])=[CH:18][N:17]=3)[CH:3]=[CH:4][C:5]=2[O:9]1)=[O:11]

Participants

3

Reactant 2

HCID 220602142-chloro-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-4-pyrimidineamineHCID 22060823Methyl 5-amino-2,3-dihydrobenzofuran-2-carboxylate

Product 1

HCID 22060965(+/-)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

Procedure

In like manner to the preparation of (±)-N4-(3,4-difluorophenyl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine, the reaction of (±)-5-amino-2,3-dihydro-2-methoxycarbonylbenzofuran with 2-chloro-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine gave (±)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-N4-(3,4-difluoromethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine. 1H NMR (DMSO-d6): δ 10.36 (bs, 1H), 9.93 (bs, 1H), 8.22 (d, 1H, J=4.8 Hz), 7.91 (bs, 1H), 7.38 (m, 3H), 7.15 9 bd, 1H, J=8.7 Hz), 6.79 (d, 1H, J=6.0 Hz), 5.33 (dd, 1H, J=6.3 and 6.6 Hz), 3.69 (s, 3H), 3.50 (dd, 1H, J=10.5 and 10.8 Hz), 3.22 (dd, 1H, J=6.0 Hz); LCMS: purity: 100%; MS (m/e): 461 (MH+).

Workup

  1. customIn like manner to the preparation of (±)-N4-(3,4-difluorophenyl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine

Sources & evidence

ORD record
ord-a96f6867bb6a47b1be615fb8e8ccc754
Source dataset
uspto-grants-2015_10
Patent number
US09162989B2

Reaction notes

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