(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 1008983Notes

Reaction equation

HRID 1008983 reaction equation
[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

Participants

9

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolvent2×HCID 8471TriethylamineSolvent

Procedure

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)+;

Workup

  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%)

Sources & evidence

ORD record
ord-1136a6c778fe4a359fc693d2ce4a7f7f
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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