(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 1008983노트

반응식

HRID 1008983 반응식
[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

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 3

HCID 180Acetone용매HCID 887Methanol용매2회HCID 8471Triethylamine용매

실험 절차

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)+;

후처리

  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%)

출처 및 근거

ORD 기록
ord-1136a6c778fe4a359fc693d2ce4a7f7f
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07973026B2

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