Hydrochloric Acid → HCID 178522587, compound

HRID 1611427Notes

Reaction equation

HRID 1611427 reaction equation
[C:1]1([S:7]([NH:10][CH2:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([NH:20][C:21]3[CH2:29][C@H:28]4[C@H:23]([CH2:24][CH2:25][C:26]5[CH:33]=[C:32]([O:34]C)[CH:31]=[CH:30][C:27]=54)[N:22]=3)=[O:19])[CH2:14][CH2:13]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B(Br)(Br)Br.Cl>ClCCl.CO>[C:1]1([S:7]([NH:10][CH2:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([NH:20][C:21]3[CH2:29][C@H:28]4[C@H:23]([CH2:24][CH2:25][C:26]5[CH:33]=[C:32]([OH:34])[CH:31]=[CH:30][C:27]=54)[N:22]=3)=[O:19])[CH2:14][CH2:13]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 178487175HCID 178487175, compound

Product 1

HCID 178522587HCID 178522587, compoundYield 47.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of trans-4-[[(phenylsulfonyl)amino]methyl]-N-(cis-3a,4,5,9b-tetrahydro-7-methoxy-1H-benz[e]indol-2-yl)cyclohexanecarboxamide (7) (0.200 g, 0.403 mmol) in dichloromethane (2 mL) was added dropwise with stirring, to a solution of boron tribromide (1.6 mmol) in dichloromethane (12 mL) at 0° C. The resultant suspension was stirred at 0° C. for 30 min. Methanol (˜1 mL) was added at which point the mixture became a clear yellow solution. The solution was stirred for 30 min at 0° C. The solvents were evaporated in vacuo, and the residue was purified by preparative HPLC on C18 reverse phase column, using water/acetonitrile/trifluoroacetic acid (50:50:0.1) as the eluent. The product obtained was dissolved in a minimum amount of methanol and converted to the hydrochloride salt by treatment with ethanolic hydrogen chloride. The solvents were evaporated in vacuo and the residue was triturated with diethyl ether to give trans-4-[[(phenylsulfonyl)amino]methyl]-N-(cis-3a,4,5,9b-tetrahydro-7-hydroxy-1H-benz[e]indol-2-yl)cyclohexanecarboxamide (9) as a beige solid (0.093 g, 45%). NMR (DMSO-d6): δ 0.77-0.95 (m, 2 H), 1.20-1.37 (m, 3 H), 1.64-1.80 (m, 2 H), 1.83-1.98 (m, 3 H), 2.43-2.64 (m, 5 H), 2.91 (d of d, 1 H), 3.48-3.74 (m, 4 H), 4.37-4.47 (m, 1 H), 6.54 (d, 1 H), 6.65 (d of d, 1 H), 7.03 (d, 1 H), 7.53-7.83 (m, 6 H), 9.37 (br s, 1 H), 11.56 (br s, 1 H), 13.22 (br s, 1 H); MS 482 (M+H)+ (Example 3).

Workup

  1. additionwas added dropwise
  2. customThe solvents were evaporated in vacuo
  3. customthe residue was purified by preparative HPLC on C18 reverse phase column
  4. customThe product obtained
  5. customThe solvents were evaporated in vacuo
  6. customthe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-958fc676514b4603bdc91fd3faaa4e79
Source dataset
uspto-grants-2006_01
Patent number
US06987188B2

Reaction notes

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