Sodium Methoxide → HCID 15947330, compound

HRID 1008981Notes

Reaction equation

HRID 1008981 reaction equation
C[O-].[Na+].[CH:4]1([C:10]2[C:11]3[S:34][C:33]([C:35]([O:37]C)=[O:36])=[CH:32][C:12]=3[N:13]3[C:20]=2[C:19]2[S:21][CH:22]=[CH:23][C:18]=2[CH2:17][N:16]([CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[C:15](=O)[CH2:14]3)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1>C1COCC1>[CH:4]1([C:10]2[C:11]3[S:34][C:33]([C:35]([OH:37])=[O:36])=[CH:32][C:12]=3[N:13]3[C:20]=2[C:19]2[S:21][CH:22]=[CH:23][C:18]=2[CH2:17][N:16]([CH2:24][CH2:25][N:26]([CH2:27][CH3:28])[CH2:29][CH3:30])[CH2:15][CH2:14]3)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 67298679HCID 67298679, compound

Product 1

HCID 15947330HCID 15947330, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Methyl 6-cyclohexyl-5-(3-formyl-2-thienyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate and N,N-diethylaminoethylamine (10 eq.) were dissolved in THF (0.08 M) and the pH adjusted with AcOH to 6; the solution was left stirring for 4 h, then all volatiles were evaporated i. vac. The residual oil was dissolved in MeOH (0.08M), NaCNBH3 (4 eq.) was added, and the mixture was stirred overnight at RT to give methyl 6-cyclohexyl-5-[3-({[2-(diethylamino)ethyl]amino}methyl)-2-thienyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate. Under the reaction conditions the latter partially closed to afford methyl 12-cyclohexyl-5-[2-(diethylamino)ethyl]-6-oxo-4,5,6,7-tetrahydrothieno[2,3-f]thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]diazocine-10-carboxylate; to drive this reaction to completion a catalytic amount of NaOMe was added and stirring was continued at 40° C. for 4 days. To a 0.05M solution of the foregoing amide in dry THF a 2M solution of borane-dimethylsulfide complex (13 eq.) in THF was added and the mixture was stirred for 1 h; after evaporation of all volatiles the residue containing (methyl 12-cyclohexyl-5-[2-(diethylamino)ethyl]-4,5,6,7-tetrahydrothieno[2,3-f]thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]diazocine-10-carboxylate) was suspended in MeOH (0.03M) and water. The pH was adjusted with LiOH to 9. The solution was left stirring at RT. Then an excess of 1N KOH-solution was added and the mixture was warmed to 50° C. and stirred for 2 h; the title compound (24%) was isolated by prep RP-HPLC. 1H-NMR (400 MHz, DMSO-d6, 330 K, δ) 7.67 (d, 1H, J 5.1), 7.18 (d, 1H, J 5.1), 3.15-3.12 (m, 2H), 3.09-3.05 (m, 5H), 2.87-2.81 (m, 2H), 1.79-1.63 (m, 8H), 1.30-1.10 (m, 14H); MS (ES+) m/z 486 (M+H)+.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 1 h
  3. customafter evaporation of all volatiles the residue
  4. additioncontaining (methyl 12-cyclohexyl-5-[2-(diethylamino)ethyl]-4,5,6,7-tetrahydrothieno[2,3-f]thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]diazocine-10-carboxylate)
  5. waitThe solution was left
  6. stirringstirring at RT
  7. additionThen an excess of 1N KOH-solution was added
  8. stirringstirred for 2 h

Sources & evidence

ORD record
ord-49ff14697900411cbe6381e837163deb
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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