Acetic Acid → Pamiparib

HRID 1775247Notes

Reaction equation

HRID 1775247 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:20](OC)=[O:21])[C:5]2[C:6]3[C:17](=O)[CH2:16][N:15]4[C@:11]([CH3:19])([CH2:12][CH2:13][CH2:14]4)[C:7]=3[NH:8][C:9]=2[CH:10]=1.C(O)(=O)C.O.[NH2:29][NH2:30].O>CO>[F:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:30][N:29]=[C:17]3[CH2:16][N:15]4[CH2:14][CH2:13][CH2:12][C@:11]4([CH3:19])[C:7]4[NH:8][C:9]([CH:10]=1)=[C:5]2[C:6]=43

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 89669848HCID 89669848, compound

Product 1

HCID 135565554PamiparibYield 94.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of compound (R)-methyl 9-fluoro-11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate (90 mg), acetic acid (0.54 g), and hydrazine hydrate (0.28 g) in methanol (30 mL) was heated at reflux. After 5 h, the reaction was cooled and water (5 mL) was added. The mixture was extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine (10 mL) and dried over MgSO4. The mixture was filtered, and the filtrate was evaporated to dryness, and the residue was purified by Pre-TLC using CH2Cl2 as eluent to give 80 mg of (R)-2-fluoro-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 11.9 (s, 1H), 10.2 (s, 1H), 7.30 (d, 1H, J=9.6 Hz), 7.20 (d, 1H, J=10.2 Hz), 3.76 (d, 1H, J=16.4 Hz), 3.34 (d, 1H, J=16.4 Hz), 2.99-3.02 (m, 1H), 2.54-2.58 (m, 1H), 2.35-2.40 (m, 1H), 1.90-1.94 (m, 1H), 1.73-1.75 (m, 1H), 1.48 (s, 3H), and 1.43-1.45 (m, 1H). MS (ESI) m/e [M+1]+ 299.

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. customthe filtrate was evaporated to dryness
  8. customthe residue was purified by Pre-TLC

Sources & evidence

ORD record
ord-20ae6badf680496583a3887840556e43
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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