Hydrochloric Acid → HCID 15948896, compound

HRID 1008965Notes

Reaction equation

HRID 1008965 reaction equation
[CH:1]1([C:7]2[C:8]3[S:30][C:29]([C:31]([O:33]C(C)(C)C)=[O:32])=[CH:28][C:9]=3[N:10]3[CH2:17][C:16](=O)[N:15]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:14][C:13]4[CH:24]=[CH:25][CH:26]=[CH:27][C:12]=4[C:11]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.B.CSC.Cl.CO>C1COCC1>[CH:1]1([C:7]2[C:8]3[S:30][C:29]([C:31]([OH:33])=[O:32])=[CH:28][C:9]=3[N:10]3[CH2:17][CH2:16][N:15]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:14][C:13]4[CH:24]=[CH:25][CH:26]=[CH:27][C:12]=4[C:11]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 12423031(Dimethyl sulfide)trihydroboronHCID 67298607HCID 67298607, compound

Product 1

HCID 15948896HCID 15948896, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 13-cyclohexyl-6-[2-(dimethylamino)ethyl]-7-oxo-5,6,7,8-tetrahydrothieno[2′,3′:4,5]pyrrolo[2,1-a][2,5]benzodiazocine-11-carboxylate (1 eq., prepared as described in Example 1, Step 5) in dry THF (0.14 M) was treated with borane-dimethylsulfide complex (20 eq., 2 M solution in THF) overnight at RT. A solution of HCl in methanol (40 eq., 1.25 M) was added to the reaction mixture, which was then heated to reflux for 1 h. All volatiles were evaporated in vacuo and the residual material was subjected to RP-HPLC purification (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) afforded the title compound after lyophilisation as a colourless powder (33%). 1H-NMR (500 MHz, DMSO-d6, 330 K, δ) 7.91 (s, 1H), 7.63 (d, J 7.1, 1H), 7.52-7.46 (m, 2H), 7.37 (d, J 6.3, 1H), 4.40 (dd, J 15.3, 4.9, 1H), 3.86 (d, J 13.9, 1H), 3.70-3.10 (m, 4H, hidden by the H2O signal), 3.05 (d, J 13.9, 1H), 3.04-2.84 (m, 2H), 2.84 (m, 6H), 2.69-2.60 (m, 1H) 2.55-2.50 (m, 1H, partially hidden by the DMSO signal), 2.02-1.09 (m, 10H). MS (ES+) m/z: 452 [M+H]+.

Workup

  1. temperaturewas then heated
  2. temperatureto reflux for 1 h
  3. customAll volatiles were evaporated in vacuo
  4. customthe residual material was subjected to RP-HPLC purification (column

Sources & evidence

ORD record
ord-4ac315dbf51a42ceb070c9946ed4ff19
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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