Acetic Acid → HCID 136242934, compound

HRID 1775243Notes

Reaction equation

HRID 1775243 reaction equation
[CH3:1][C@@:2]12[C:10]3[NH:11][C:12]4[CH:13]=[CH:14][CH:15]=[C:16]([C:18]([O:20]C)=O)[C:17]=4[C:9]=3[C:8](=O)[CH2:7][N:6]1[CH2:5][CH2:4][CH2:3]2.C(O)(=O)C.O.[NH2:28][NH2:29].O>CO>[CH3:1][C@:2]12[CH2:3][CH2:4][CH2:5][N:6]1[CH2:7][C:8]1[C:9]3[C:17]4[C:16]([C:18](=[O:20])[NH:28][N:29]=1)=[CH:15][CH:14]=[CH:13][C:12]=4[NH:11][C:10]=32

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 89669847HCID 89669847, compound

Product 1

HCID 136242934HCID 136242934, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of compound (R)-methyl 11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate (58 mg, 0.19 mmol), acetic acid (0.4 mL), and hydrazine hydrate (0.2 mL) in methanol (10 mL) was heated at reflux. After 7 h, the reaction was cooled and water (5 mL) was added. The mixture was extracted with EtOAc (3×5 mL) and the combined organic layers were washed with brine (10 mL) and dried over MgSO4. The mixture was filtered, evaporated to dryness, and the residue was purified by Pre-TLC using CH2Cl2 as eluent to give 40 mg of (R)-10a-methyl-7,8,9,10,10a, 11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one. 1H NMR (DMSO-d6) δ 12.9 (s, 1H), 10.6 (s, 1H), 7.50-7.52 (m, 2H), 7.12 (t, 1H, J=7.8 Hz), 3.24-3.26 (m, 1H), 2.91 (d, 1H, J=18.4 Hz), 2.37-2.38 (m, 1H), 2.30-2.32 (m, 1H), 2.20-2.21 (m, 1H), 1.95-1.96 (m, 1H), 1.41-1.43 (m, 1H), 1.34 (s, 3H), and 1.18-1.19 (m 1H). MS (ESI) m/e [M+1]+ 281.0.

Workup

  1. temperatureat reflux
  2. temperaturethe reaction was cooled
  3. extractionThe mixture was extracted with EtOAc (3×5 mL)
  4. washthe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationThe mixture was filtered
  7. customevaporated to dryness
  8. customthe residue was purified by Pre-TLC

Sources & evidence

ORD record
ord-f3ebb10f5c1543e6b5bc6df3821ec1ff
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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