2-Methyltetrahydrofuran → HCID 178480320、化合物

HRID 874074ノート

反応式

HRID 874074 の反応式
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][NH2:16])[CH:10]=[N:11][CH:12]=1.[C:17]([O:21][C:22]([C@H]1CC[C@H](C(O)=O)CC1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(P1(=O)OP(CCC)(=O)OP(C[CH2:48][CH3:49])(=O)O1)CC.CC[N:53](CC)CC.[CH3:58][CH:59]1[CH2:63][CH2:62][CH2:61][O:60]1>>[NH3:2].[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][NH:16][C:61]([C@H:62]2[CH2:49][CH2:48][C@H:58]([NH:53][C:22](=[O:23])[O:21][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:59][CH2:63]2)=[O:60])[CH:10]=[N:11][CH:12]=1

参加物

7

反応物 5

HCID 73012-MethyltetrahydrofuranHCID 8471TriethylamineHCID 111923Propylphosphonic anhydride2 回HCID 54675475(S)-3-(5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)propan-1-amineHCID 178451160HCID 178451160、化合物

生成物 2

HCID 222AmmoniaHCID 178480320HCID 178480320、化合物収率 64%

実験手順

A solution of 3-{5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}propan-1-amine (preparation 4) (100 mg, 0.45 mmol) in 2-methyltetrahydrofuran (2 ml) was treated, with stirring, with trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid (132 mg, 0.502 mmol) followed by T3P (580 μl, 0.91 mmol) and then Et3N (118 μl, 0.91 mmol). After stirring for 3 hours, the solution was treated with T3P (240 μL, 0.38 mmol). After stirring for 18 hours the solution was concentrated in vacuo and the residue was taken up in MeOH and applied to an SCX-2 cartridge which was eluted with MeOH followed by ammonia in MeOH (˜2M). Product containing fractions were concentrated in vacuo and the residue purified by column chromatography on silica gel eluting with EtOAc:MeOH:NH3 (gradient from 1:0:0 to 90:10:1) to give the title compound as a gum (130 mg, 64%).

後処理

  1. stirringAfter stirring for 18 hours the solution
  2. concentrationwas concentrated in vacuo
  3. washwas eluted with MeOH
  4. additionProduct containing fractions
  5. concentrationwere concentrated in vacuo
  6. customthe residue purified by column chromatography on silica gel eluting with EtOAc

出典と根拠

ORDレコード
ord-19d8398e3a684a67946b7e3eed3e61a4
出典データセット
uspto-grants-2015_03
特許番号
US08980276B2

反応ノート

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