(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → methyl 6-cyclohexyl-5-[2-({[(3S)-1-isopropylpyrrolidin-3-yl]amino}methyl)phenyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008983ノート

反応式

HRID 1008983 の反応式
[CH:1]1([C:7]2[C:8]3[S:27][C:26]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][C:9]=3[N:10]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH:18]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.Cl.[CH:34]([N:37]1[CH2:41][CH2:40][C@H:39]([NH2:42])[CH2:38]1)([CH3:36])[CH3:35].C(OC(N[C@H]1CCNC1)=O)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH3-]C#N.[Na+]>CO.CCN(CC)CC.CC(C)=O>[CH:1]1([C:7]2[C:8]3[S:27][C:26]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][C:9]=3[N:10]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:18][NH:42][C@H:39]2[CH2:40][CH2:41][N:37]([CH:34]([CH3:36])[CH3:35])[CH2:38]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

9

反応物 5

HCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 67298942(3S)-1-(propan-2-yl)pyrrolidin-3-amine dihydrochlorideHCID 86629783methyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

生成物 1

HCID 67298536methyl 6-cyclohexyl-5-[2-({[(3S)-1-isopropylpyrrolidin-3-yl]amino}methyl)phenyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

試薬・触媒・溶媒 3

HCID 180Acetone溶媒HCID 887Methanol溶媒2 回HCID 8471Triethylamine溶媒

実験手順

Methyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate was dissolved in MeOH (0.05M) and (3S)-1-isopropylpyrrolidin-3-amine dihydrochloride (1.2 eq.; prepared in two steps from commercial (S)-3-(tert.-butyloxycarbonylamino)pyrrolidine by reductive amination with acetone and acidic cleavage of the protecting group) in MeOH was added. The pH was adjusted with sodium triacetoxyborohydride and NEt3 to 5. The mixture was left stirring for 2 h, then NaCNBH3 (2 eq.) was added and stirring was continued for 3 h. All volatiles were evaporated i. vac, the residual material was purified by chromatography (EtOAc+1% NEt3, then EtOAc+1% NEt3+10% MeOH). After evaporation of the solvents a glassy solid was obtained (84%). 1H-NMR (400 MHz, CDCl3, 300 K, δ) 7.62 (s, 1H), 7.55 (dd 1H, J2 7.23, J3 2.85), 7.45 (dt, 1H, J2 7.45, J3 0.87), 7.33 (t, 1H, J 7.46), 7.21 (d, 1H, J 7.45), 4.48 (2d, 2H, J 3.95, J 2.85), 3.90 (s, 3H), 3.67 (s, 3H), 3.53-3.51 (m, 2H), 3.20-3.18 (m, 1H), 2.80-2.76 (m, 1H), 2.57-2.52 (m, 2H), 2.30-2.19 (m, 2H), 2.13-1.10 (m, 14H), 1.05-1.01 (m, 6H); MS (ES+) m/z 552 (M+H)+;

後処理

  1. additionwas added
  2. waitThe mixture was left
  3. stirringstirring
  4. waitwas continued for 3 h
  5. customAll volatiles were evaporated i
  6. customvac, the residual material was purified by chromatography (EtOAc+1% NEt3
  7. customAfter evaporation of the solvents a glassy solid
  8. customwas obtained (84%)

出典と根拠

ORDレコード
ord-1136a6c778fe4a359fc693d2ce4a7f7f
出典データセット
uspto-grants-2011_07
特許番号
US07973026B2

反応ノート

読み込み中…