2-Methyltetrahydrofuran → HCID 178480322、化合物

HRID 874076ノート

反応式

HRID 874076 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]([O: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>>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([O: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

6

反応物 5

HCID 73012-MethyltetrahydrofuranHCID 8471TriethylamineHCID 111923Propylphosphonic anhydride2 回HCID 54675478(S)-2-(5-(1-methylpyrrolidin-2-yl)pyridin-3-yloxy)ethanamineHCID 178451160HCID 178451160、化合物

生成物 1

HCID 178480322HCID 178480322、化合物収率 35%

実験手順

A solution of 2-({5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}oxy)ethanamine (preparation 12) (55 mg, 0.25 mmol) in 2-methyltetrahydrofuran (2 ml) was treated, with stirring, with trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid (91 mg, 0.373 mmol) followed by T3P (317 μl, 0.498 mmol) and the Et3N(118 μl, 0.91 mmol). After stirring for 3 hours, the solution was treated with T3P (69 μL, 0.498 mmole). 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 methanol 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). This material was then dissolved in DCM and treated with PS-Isocyanate resin for 3 hours then filtered and evaporated in-vacuo to give the title compound as a pale yellow gum (35 mg, 35%);

後処理

  1. stirringAfter stirring for 18 hours the solution
  2. concentrationwas concentrated in vacuo
  3. washwas eluted with methanol
  4. additionProduct containing fractions
  5. concentrationwere concentrated in vacuo
  6. customthe residue purified by column chromatography on silica gel eluting with EtOAc
  7. dissolutionThis material was then dissolved in DCM
  8. additiontreated with PS-Isocyanate resin for 3 hours
  9. filtrationthen filtered
  10. customevaporated in-vacuo

出典と根拠

ORDレコード
ord-05e2c4e52103451a93a8a4c08ef17ead
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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