Methyl 5-amino-2,3-dihydrobenzofuran-2-carboxylate → (+)-N4-(3,4-difluorophenyl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine

HRID 528377Notes

Reaction equation

HRID 528377 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=2)[C:5]([F:17])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]2[O:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24][C:23]=2[CH:31]=1>CO>[F:16][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[C:5]([F:17])=[CH:4][N:3]=[C:2]([NH:18][C:19]3[CH:20]=[CH:21][C:22]4[O:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24][C:23]=4[CH:31]=3)[N:7]=2)[CH:14]=[CH:13][C:12]=1[F:15]

Participants

4

Reactant 2

HCID 22060823Methyl 5-amino-2,3-dihydrobenzofuran-2-carboxylateHCID 220610492-chloro-N4-(3,4-difluorophenyl)-5-fluoro-4-pyrimidineamine

Product 1

HCID 22060930(+)-N4-(3,4-difluorophenyl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of equivalent amount of 2-chloro-N4-(3,4-difluorophenyl)-5-fluoro-4-pyrimidineamine and (±)-5-amino-2,3-dihydro-2-methoxycarbonylbenzofuran in MeOH was shaken in a sealed tube at 80° C. for 48 h, cooled to room temperature and diluted with a mixture of n-hexanes:EtOAc (1:1; v/v). The resulting solid formed was filtered, washed with a mixture of EtOAc:n-hexanes (1:1; v/v), dried and analyzed to give (±)-N4-(3,4-difluorophenyl)-N2-(2,3-dihydro-2-methoxycarbonylbenzofuran-5-yl)-5-fluoro-2,4-pyrimidinediamine. 1H NMR (DMSO-d6): δ 10.21 (bs, 1H), 9.80 (bs, 1H), 8.20 (d, 1H, J=4.8 Hz), 7.94 (bs, 1H), 7.43 (m, 3H0, 7.15 (bd, 1H, J=8.4 Hz), 6.81 (d, 1H, J=8.1 Hz), 5.35 (dd, 1H, J=6.0 and 6.3 Hz), 3.69 (s, 3H), 3.52 (dd, 1H, J=10.5), 3.22 (dd, 1H, J=9.0 and 6.0 Hz); LCMS: purity: 99%; MS (m/e): 417 (MH+).

Workup

  1. temperaturecooled to room temperature
  2. customThe resulting solid formed
  3. filtrationwas filtered
  4. washwashed with a mixture of EtOAc:n-hexanes (1:1; v/v)
  5. customdried

Sources & evidence

ORD record
ord-cf315a16b47e4a03806c5b5a3f58699f
Source dataset
uspto-grants-2016_05
Patent number
US09346765B2

Reaction notes

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