Benzylamine → HCID 12147288, compound

HRID 1582446Notes

Reaction equation

HRID 1582446 reaction equation
[CH2:1]([N:8]1[CH2:24][CH2:23][C:12]2=[C:13]([CH2:20][CH2:21]O)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[N:11]2[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(N(CC)CC)C.[CH2:37]([NH2:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(#N)C>[CH2:37]([NH:44][CH2:21][CH2:20][C:13]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[N:11]2[CH2:10][CH2:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:24][CH2:23][C:12]=12)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 10268002HCID 10268002, compound

Product 1

HCID 12147288HCID 12147288, compoundYield 53.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-(3-benzyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-1-ethanol (320 mg, 1.0 mmol) in dichloromethane (10 mL) is cooled to 0° C., treated with methanesulfonyl chloride (93 μL, 1.2 mmol), and triethylamine (0.21 mL, 1.5 mmol). After 30 min, the yellow solution is diluted with additional dichloromethane (15 mL) and washed once with water (15 mL), once with brine (15 mL), dried over MgSO4, filtered, and concentrated to give a yellow oil. This crude material is diluted with acetonitrile (10 mL) and treated with benzylamine (0.33 mL, 3.0 mmol), and powdered potassium carbonate (415 mg, 3.0 mmol) followed by heating to reflux. After 18 hrs, the yellow suspension is cooled to rt, concentrated, diluted with water (15 mL), and extracted twice with dichloromethane (20 mL). The combined organics are washed with brine (20 mL), dried over MgSO4, filtered, and concentrated to give a crude oil. This material is purified by LC (230-400 silica gel) eluting with 4:0.5:95.5 methanol/NH4OH/dichloromethane to afford 220 mg of N-benzyl-2-(3-benzyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-1-ethanamine as a yellow oil. IR (liq.) 3025, 2913, 2811, 1494, 1478, 1469, 1453, 1427, 1372, 1363, 1347, 1324, 1120, 733, 698 cm−1; MS (EI) m/z 409 (M+).

Workup

  1. washwashed once with water (15 mL), once with brine (15 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a yellow oil
  6. temperatureby heating to reflux
  7. waitAfter 18 hrs
  8. concentrationconcentrated
  9. additiondiluted with water (15 mL)
  10. extractionextracted twice with dichloromethane (20 mL)
  11. washThe combined organics are washed with brine (20 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give a crude oil
  16. customThis material is purified by LC (230-400 silica gel)
  17. washeluting with 4:0.5:95.5 methanol/NH4OH/dichloromethane

Sources & evidence

ORD record
ord-ae282519195b409a981000424c74e123
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

Loading…