P-Anisidine → HCID 9968992, compound

HRID 1582449Notes

Reaction equation

HRID 1582449 reaction equation
FC(F)(F)C([N:5]1[CH2:18][CH2:17][C:9]2=[CH:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6]1)=O.[C:21](Cl)(=[O:25])[C:22](Cl)=[O:23].[CH3:27][O:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1.C(N(CC)CC)C>ClCCl>[CH3:27][O:28][C:29]1[CH:35]=[CH:34][C:32]([NH:33][C:21](=[O:25])[C:22](=[O:23])[C:10]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[N:8]3[CH2:7][CH2:6][NH:5][CH2:18][CH2:17][C:9]=23)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 7732P-AnisidineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 9921822HCID 9921822, compound

Product 1

HCID 9968992HCID 9968992, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(Chart B, Step 1): A solution 3-(trifluoroacetyl)-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole in dichloromethane (20 mL) is cooled to 0° C. and treated with oxalylchloride (0.17 mL, 2.0 mmol) instantly becoming a yellow color. After 40 min, the reaction mixture is warmed to rt and volatiles are removed under reduced pressure. The resulting solid is diluted with toluene (20 mL) and dichloromethane (5 mL) and treated with the 4-methoxy aniline (160 mg, 1.3 mmol) and triethylamine (0.42 mL, 3.0 mmol) with immediate smoke/haze forming. After 18 hrs, the reaction mixture is concentrated, diluted with methanol (10 mL) and THF (10 mL) and treated with 1N sodium hydroxide (10 mL). After 15 min, reaction mixture is concentrated, diluted with 1N sodium hydroxide (20 mL), and extracted twice with dichloromethane (25 mL). The combined organics are washed with brine (25 mL), dried over MgSO4, filtered, and concentrated to give a crude solid. This material is purified by LC (230-400 silica gel) eluting with 10% methanol/dichloromethane to afford 359 mg of N-(4-methoxyphenyl)-2-oxo-2-(2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)acetamide as a light yellow solid, mp 177-180° C. IR (drift) 1670, 1621, 1559, 1507, 1465, 1416, 1333, 1264, 1242, 1221, 1211, 1073, 838, 789, 762 cm−1; OAMS supporting ions at: ESI+364.1.

Workup

  1. customvolatiles are removed under reduced pressure
  2. additionThe resulting solid is diluted with toluene (20 mL) and dichloromethane (5 mL)
  3. customforming
  4. waitAfter 18 hrs
  5. concentrationthe reaction mixture is concentrated
  6. additiondiluted with methanol (10 mL) and THF (10 mL)
  7. additiontreated with 1N sodium hydroxide (10 mL)
  8. waitAfter 15 min
  9. customreaction mixture
  10. concentrationis concentrated
  11. additiondiluted with 1N sodium hydroxide (20 mL)
  12. extractionextracted twice with dichloromethane (25 mL)
  13. washThe combined organics are washed with brine (25 mL)
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto give a crude solid
  18. customThis material is purified by LC (230-400 silica gel)
  19. washeluting with 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-9a26ed0b9c334d00a3cd1c7f33c7b875
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

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