Carbamate → 5-Methyl-1-[2-(pyridin-2-ylmethyloxy)3-methylpyridin-5-ylcarbamoyl]-6-trifluoromethylindoline

HRID 427737ノート

反応式

HRID 427737 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH3:16])[C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[N:6][CH:7]=1.Cl[C:18](OC1C=CC=CC=1)=O.[C:27](=[O:30])([O-])[NH2:28].CO[C:33]1[C:34]([C:45]([F:48])([F:47])[F:46])=[CH:35][C:36]([N+]([O-])=O)=[C:37]([CH2:39][C:40]#N)[CH:38]=1>ClCCl.CN(C=O)C.CO.ClCCl.C(N(CC)CC)C>[CH3:18][C:33]1[CH:38]=[C:37]2[C:36](=[CH:35][C:34]=1[C:45]([F:48])([F:47])[F:46])[N:28]([C:27](=[O:30])[NH:1][C:2]1[CH:3]=[C:4]([CH3:16])[C:5]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)=[N:6][CH:7]=1)[CH2:40][CH2:39]2

参加物

9

反応物 4

HCID 276CarbamateHCID 15891Phenyl chloroformateHCID 107777195-Methoxy-2-nitro-4-(trifluoromethyl)benzene acetonitrileHCID 183577225-Amino-3-methyl-2(pyridin-2-ylmethyloxy)pyridine

生成物 1

HCID 183577305-Methyl-1-[2-(pyridin-2-ylmethyloxy)3-methylpyridin-5-ylcarbamoyl]-6-trifluoromethylindoline収率 28%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回HCID 8471Triethylamine溶媒2 回HCID 21226129Dichloromethane methanol溶媒

実験手順

5-Amino-3-methyl-2(pyridin-2-ylmethyloxy)pyridine (D15, 0.5 g, 2.3 mmol) in dichloromethane (30 ml) was cooled to −20° C. under argon. Triethylamine (0.32 ml, 2.3 mmol) was added, followed dropwise by phenyl chloroformate (0.35 ml, 2.8 mmol). The mixture was warmed to room temperature and diluted with dichloromethane (100 ml) then washed with aqueous sodium bicarbonate (50 ml), dried (Na2SO4) and evaporated in vacuo to give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate. The crude carbamate was treated with 5-methyl-6-trifluoromethylindoline (D7, 0.47 g, 0.0023 mol, 1 eq) and triethylamine (1 ml) in DMF (30 ml) at 100° C. under argon for 2 hours then allowed to cool. Solvent was removed in vacuo and the residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml). The combined organics were dried (Na2SO4) and evaporated in vacuo to give the crude product which was subjected to flash chromatography using 5% methanol/dichloromethane as eluant and recrystallised from dichloromethane/60-80° C. petroleum ether to afford the title compound (0.27 g, 28%) as white crystals. m.p. 188-189° C.

後処理

  1. washthen washed with aqueous sodium bicarbonate (50 ml)
  2. dry with materialdried (Na2SO4)
  3. customevaporated in vacuo
  4. customto give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate
  5. temperatureto cool
  6. customSolvent was removed in vacuo
  7. customthe residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml)
  8. dry with materialThe combined organics were dried (Na2SO4)
  9. customevaporated in vacuo
  10. customto give the crude product which
  11. customrecrystallised from dichloromethane/60-80° C. petroleum ether

出典と根拠

ORDレコード
ord-0e3303ad32ac4c58b69515ab2db75dbc
出典データセット
uspto-grants-2001_11
特許番号
US06313145B1

反応ノート

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