Methanol → HCID 178479778, compound

HRID 1611428Notes

Reaction equation

HRID 1611428 reaction equation
B(Br)(Br)Br.[ClH:5].C[O:7][C:8]1[CH:39]=[CH:38][C:11]2[C@@H:12]3[C@H:16]([CH2:17][CH2:18][C:10]=2[CH:9]=1)[N:15]=[C:14]([NH:19][CH2:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([CH2:27][NH:28][S:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])[CH2:23][CH2:22]1)[CH2:13]3.C(N(CC)CC)C.CO>ClCCl>[ClH:5].[OH:7][C:8]1[CH:39]=[CH:38][C:11]2[C@@H:12]3[C@H:16]([CH2:17][CH2:18][C:10]=2[CH:9]=1)[N:15]=[C:14]([NH:19][CH2:20][C@H:21]1[CH2:22][CH2:23][C@H:24]([CH2:27][NH:28][S:29]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)(=[O:31])=[O:30])[CH2:25][CH2:26]1)[CH2:13]3

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 25134Boron tribromideHCID 178487174HCID 178487174, compound

Product 1

HCID 178479778HCID 178479778, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of boron tribromide (3.4 mmol) in dichloromethane (3.4 mL) was added to a solution of N-[[trans-4-[[(cis-3a,4,5,9b-tetrahydro-7-methoxy-1H-benz[e]indol-2-yl)amino]methyl]cyclohexyl]methyl]benzenesulfonamide hydrochloride (8) (0.37 g, 0.714 mmol) and triethylamine (0.235 mL, 1.69 mmol) in dichloromethane (20 mL) at 0° C. The resultant mixture was stirred at 0° C. for 1 h, and stirring was continued at room temperature for an additional 1 h. The mixture was cooled on an ice bath and methanol was added. After stirring for several minutes, the solvents were evaporated in vacuo. The residue was purified by preparative HPLC on a C18 reverse phase column, eluted with water/acetonitrile/trifluoroacetic acid (˜50:50:0.1). The product was dissolved in a minimum amount of methanol and converted to the hydrochloride salt with ethanolic hydrogen chloride. The solvents were evaporated in vacuo to give N-[[trans-4-[[(cis-3a,4,5,9b-tetrahydro-7-hydroxy-1H-benz[e]indol-2-yl)amino]methyl]cyclohexyl]methyl]benzenesulfonamide hydrochloride as a colorless solid (0.15 g, 42%). NMR (DMSO-d6): δ 0.67-0.98 (m, 4 H), 1.21-1.50 (m, 2 H), 1.58-1.97 (m, 6 H), 2.50-2.75 (m, 5 H), 3.03-3.23 (m, 2 H), 3.31-3.46 (m, 1 H), 3.55-3.67 (m, 1 H), 4.17-4.33 (m, 1 H), 6.53 (s, 1 H), 6.64 (d, 1 H), 6.99 (d, 1 H), 7.52-7.83 (m, 6 H), 9.34 (br s, 1 H), 9.76 (br s, 1 H) and 10.24 (br s, 1 H); MS 468 (M+H)+ (Example 4).

Workup

  1. temperatureThe mixture was cooled on an ice bath
  2. stirringAfter stirring for several minutes
  3. customthe solvents were evaporated in vacuo
  4. customThe residue was purified by preparative HPLC on a C18 reverse phase column
  5. washeluted with water/acetonitrile/trifluoroacetic acid (˜50:50:0.1)
  6. dissolutionThe product was dissolved in a minimum amount of methanol
  7. customThe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-cb213106e8654767a9c7845276c0464d
Source dataset
uspto-grants-2006_01
Patent number
US06987188B2

Reaction notes

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