Hydrogen Bromide → HCID 71008027, compound

HRID 1469551Notes

Reaction equation

HRID 1469551 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([CH:9]([OH:28])[CH2:10][N:11]2[C:23]3[CH2:22][CH2:21][N:20]4[CH2:24][CH2:25][CH2:26][CH:19]4[C:18]=3[C:17]3[CH:16]=[C:15]([CH3:27])[CH:14]=[CH:13][C:12]2=3)[CH:6]=[CH:5][N:4]=1.Br>>[CH3:27][C:15]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:10][CH:9]([C:7]3[CH:6]=[CH:5][NH:4][C:3](=[O:2])[CH:8]=3)[OH:28])[C:23]3[CH2:22][CH2:21][N:20]4[CH:19]([C:18]=3[C:17]=2[CH:16]=1)[CH2:26][CH2:25][CH2:24]4

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68283305HCID 68283305, compound

Product 1

HCID 71008027HCID 71008027, compoundYield 46.2%

Procedure

1-(2-Methoxy-pyridin-4-yl)-2-(9-methyl-1,2,3,4,5,10c-hexahydro-3a,6-diaza-cyclopenta[c]fluoren-6-yl)-ethanol (45 mg, 0.119 mmol) and 47% aqueous HBr (4 mL) and heated at 100° C. for 45 min. The reaction was monitored by TLC and LCMS. After consumption of starting material, the reaction mixture was cooled to RT and basified with ammonia and extracted with EtOAc (2×25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated and the crude product was purified by reverse phase chromatography to obtain 20 mg of 4-(2-(2,3,5,6-tetrahydro-10-methyl-1H-indolizino[7,8-b]indol-7(11cH)-yl)-1-hydroxyethyl)pyridin-2(1H)-one. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.43 (d, 1H), 7.23 (m, 2H), 7.05 (t, 1H), 6.7 (m, 1H), 6.5 (d, 1H), 4.79 (m, 1H), 4.3 (m, 2H), 3.9 (m, 2H), 3.8 (m, 1H), 3.6 (m, 1H), 3.4 (m, 2H), 3.1 (m, 1H), 2.6 (m, 1H), 2.4 (s, 3H), 2.3 (m, 2H), 1.9 (m, 1H). Separation by chiral HPLC provided enantiomers II-132a-b.

Workup

  1. customAfter consumption of starting material
  2. extractionextracted with EtOAc (2×25 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customthe crude product was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-e963bdfebc5b433aa6270b3261741599
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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