Water → Methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-chloro-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 711474ノート

反応式

HRID 711474 の反応式
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([NH:13][C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)[N:3]=1.[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]1[CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(N(C(C)C)C(C)C)C.O>CN(C=O)C>[C:31]([O:30][C:29]([NH:28][CH2:27][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][N:21]1[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([NH:13][C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)[N:3]=1)=[O:35])([CH3:34])([CH3:32])[CH3:33]

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2756031tert-butyl N-((piperidin-2-yl)methyl)carbamateHCID 58317610Methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylate

生成物 1

HCID 86654715Methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-chloro-6-(m-tolylamino)pyrimidine-5-carboxylate収率 32.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

A mixture of methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylate (600.6 mg, 1.924 mmol), tert-butyl piperidin-2-ylmethylcarbamate (500.9 mg, 2.337 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.4 mL, 2.296 mmol) in DMF (10 mL) was stirred at 0° C. for 3 h. Water (50 mL) was added to the mixture, which was extracted with EtOAc (2×40 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and then filtered (DM1020). The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2, hexanes/EtOAc=4/1) to give the title compound as a clear oil (310.5 mg). 1H NMR (500 MHz, CDCl3) δ ppm 1.34-1.74 (m, 15H), 2.35-2.37 (m, 3H), 3.03-3.21 (m, 2H), 3.60-3.71 (m, 1H), 3.90 (s, 3H), 4.43-5.04 (m, 3H), 6.94-6.98 (m, 1H), 7.23-7.46 (m, 3H), 10.13-10.43 (m, 1H). [M+H] calc'd for C24H33ClN5O4, 490. found, 490.

後処理

  1. extractionwas extracted with EtOAc (2×40 mL)
  2. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered (DM1020)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography (SiO2, hexanes/EtOAc=4/1)

出典と根拠

ORDレコード
ord-81c3486db4154656a3b9ebece4e34b7b
出典データセット
uspto-grants-2015_11
特許番号
US09181255B2

反応ノート

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