Hydrochloric Acid → 13-Cyclohexyl-6-methyl-5,6,7,8-tetrahydrothieno[2',3':4,5]pyrrolo[2,1-a][2,5] benzodiazocine-11-carboxylic acid

HRID 1008966Notes

Reaction equation

HRID 1008966 reaction equation
[CH:1]1([C:7]2[C:8]3[S:27][C:26]([C:28]([O:30]C(C)(C)C)=[O:29])=[CH:25][C:9]=3[N:10]([CH2:20][C:21](OC)=O)[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.[CH3:35][NH2:36].[BH4-].[Na+].B.CSC.Cl>CO.CCOC(C)=O.C1COCC1>[CH:1]1([C:7]2[C:8]3[S:27][C:26]([C:28]([OH:30])=[O:29])=[CH:25][C:9]=3[N:10]3[CH2:20][CH2:21][N:36]([CH3:35])[CH2:18][C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=4[C:11]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 12423031(Dimethyl sulfide)trihydroboronHCID 86629778tert-butyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 1594889713-Cyclohexyl-6-methyl-5,6,7,8-tetrahydrothieno[2',3':4,5]pyrrolo[2,1-a][2,5] benzodiazocine-11-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate (1 eq., prepared as described in Example 1, Step 4) in dry methanol (0.05 M) was treated with methylamine (1.5 eq., 2 M solution in THF) at RT for 1 h. Sodium borohydride (2 eq.) was then added and the mixture stirred overnight at RT. The residue was diluted with EtOAc and washed with a saturated NaHCO3 solution and with brine, then dried over sodium sulfate and evaporated in vacuo. The foregoing compound (1 eq.) was dissolved in dry THF (0.14M) was treated with borane-dimethylsulfide complex (20 eq., 2M solution in THF) overnight at RT. The reaction mixture was then treated with HCl in methanol (40 eq., 1.25 M solution) and heated to reflux for 1 h. The volatiles were evaporated in vacuo and the residue purified by RP-HPLC (column: Waters XTERRA PREP MS C18, 10 μm; solvents: A: water+0.1% trifluoroacetic acid; B: MeCN+0.1% trifluoroacetic acid; 25% B in A isocratic for 3 min, linear to 20% A in B in 12 min) to afford the title compound after lyophilisation as a colourless powder (39%). 1H-NMR (400 MHz, DMSO-d6, 300 K, δ) 12.83 (bs, 1H), 9.86 (bs, 1H), 8.05 (s, 1H), 7.94-7.90 (m, 1H), 7.65-7.60 (m, 2H), 7.48-7.45 (m, 1H), 4.66 (d, J 15.3, 1H), 4.39 (d, J 12.7, 1H), 3.70-3.20 (m, 4H, partially hidden by H2O signal), 3.06 (s, 3H), 2.50 (m, 1H, hidden by DMSO signal), 2.03-1.36 (m, 10H). MS (ES+) m/z: 395 [M+H]+.

Workup

  1. washwashed with a saturated NaHCO3 solution and with brine
  2. dry with materialdried over sodium sulfate
  3. customevaporated in vacuo
  4. temperatureheated
  5. temperatureto reflux for 1 h
  6. customThe volatiles were evaporated in vacuo
  7. customthe residue purified by RP-HPLC (column
  8. wait25% B in A isocratic for 3 min

Sources & evidence

ORD record
ord-28314cf5a028464ca69c42a9ee65d97d
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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