Dimethylformamide → HCID 22720322, compound

HRID 1582439Notes

Reaction equation

HRID 1582439 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]1[C:12]2=[CH:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[N:11]2[CH2:10][CH2:9][N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:7]1.CN([CH:30]=[O:31])C>>[CH:30]([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]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:7][CH2:6][C:12]=12)=[O:31]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 9835548HCID 9835548, compound

Product 1

HCID 22720322HCID 22720322, compound

Procedure

A solution of DMF (10 mL) cooled to 0° C. is treated with phosphorus oxychloride (0.30 mL, 3.3 mmol) and stirred for 10 min. This clear colorless solution of the cloroiminium salt is slowly treated with a solution of tert-butyl 1,2,4,5-tetrahydro-3H-[1,4]diazepino[1,7-a]indole-3-carboxylate in DMF (9 mL) followed by warming to rt. After 18 hr, the reaction is quenched with 5N sodium hydroxide (40 mL), stirred 5 min, and extracted twice with dichloromethane (40 mL). The combined organics are washed twice with water (25 mL), once with brine (25 mL), dried over MgSO4, filtered, and concentrated to give 942 mg of a crude yellow solid. This material is purified by LC (biotage 40 g column) eluting with 35% ethyl acetate/heptane to afford 677 mg of tert-butyl 11-formyl-1,2,4,5-tetrahydro-3H-[1,4]diazepino[1,7-a]indole-3-carboxylate as a pale yellow solid, mp 167-168° C. IR (drift) 1684, 1654, 1469, 1424, 1396, 1370, 1350, 1304, 1248, 1197, 1170, 1121, 762, 757, 752 cm−1.

Workup

  1. waitAfter 18 hr
  2. customthe reaction is quenched with 5N sodium hydroxide (40 mL)
  3. stirringstirred 5 min
  4. extractionextracted twice with dichloromethane (40 mL)
  5. washThe combined organics are washed twice with water (25 mL), once with brine (25 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give 942 mg of a crude yellow solid
  10. customThis material is purified by LC (biotage 40 g column)
  11. washeluting with 35% ethyl acetate/heptane

Sources & evidence

ORD record
ord-e9ad6302850b4d8b85fb755d144b676a
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

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