Acetic Acid → 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

HRID 1008980Notes

Reaction equation

HRID 1008980 reaction equation
[CH:1]1([C:7]2[C:8]3[S:26][C:25]([C:27]([O:29][CH3:30])=[O:28])=[CH:24][C:9]=3[N:10]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:11]=2[C:12]2[S:13][CH:14]=[CH:15][C:16]=2[CH:17]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N[N:34]([CH2:38][CH3:39])NCC)C.[CH3:40][C:41](O)=O.[BH3-][C:45]#[N:46].[Na+].[CH2:48]1COCC1>>[CH:1]1([C:7]2[C:8]3[S:26][C:25]([C:27]([O:29][CH3:30])=[O:28])=[CH:24][C:9]=3[N:10]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:11]=2[C:12]2[S:13][CH:14]=[CH:15][C:16]=2[CH2:17][NH:46][CH2:45][CH2:48][N:34]([CH2:38][CH3:39])[CH2:40][CH3:41])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 57254831N,N-diethylaminoethylamineHCID 86629782Methyl 6-cyclohexyl-5-(3-formyl-2-thienyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 67298553methyl 6-cyclohexyl-5-[3-({[2-(diethylamino)ethyl]amino}methyl)-2-thienyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

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. waitthe solution was left
  2. customall volatiles were evaporated i
  3. dissolutionThe residual oil was dissolved in MeOH (0.08M)
  4. stirringthe mixture was stirred overnight at RT

Sources & evidence

ORD record
ord-63731e0d925a4222a4ddf0c65888dc76
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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