2-Bromopropane → HCID 57950281, compound

HRID 930789Notes

Reaction equation

HRID 930789 reaction equation
Br[CH:2]([CH3:4])[CH3:3].Cl.[CH2:6]([O:13][C:14]1[CH:19]=[CH:18][N:17]([C:20]2[CH:28]=[C:27]3[C:23]([C:24]4[CH2:33][CH2:32][NH:31][CH2:30][C:25]=4[N:26]3[CH3:29])=[CH:22][CH:21]=2)[C:16](=[O:34])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[CH2:6]([O:13][C:14]1[CH:19]=[CH:18][N:17]([C:20]2[CH:28]=[C:27]3[C:23]([C:24]4[CH2:33][CH2:32][N:31]([CH:2]([CH3:4])[CH3:3])[CH2:30][C:25]=4[N:26]3[CH3:29])=[CH:22][CH:21]=2)[C:16](=[O:34])[CH:15]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 63582-BromopropaneHCID 10796Cesium carbonateHCID 68657416HCID 68657416, compound

Product 1

HCID 57950281HCID 57950281, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

2-Bromopropane (1.5 mL, 16 mmol) was added to a mixture of 4-(benzyloxy)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride (138 mg, 0.327 mmol) and Cs2CO3 (1.2 g, 3.7 mmol) in acetonitrile (25 mL). The mixture was stirred at 55° C. for 72 h. The resulting mixture was cooled, and the precipitate was filtered off. The mother liquor was concentrated under vacuum. The residue was purified by preparatory TLC (silica gel, 10:1:0.1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford 4-(benzyloxy)-1-(2-isopropyl-9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one. The free base was converted to the HCl salt using 1.25 M HCl in methanol to provide the title compound (26 mg, 19%) as a off white solid: 1H NMR (500 MHz, DMSO-d6) δ 10.50 (s, 1H), 7.56 (d, J=4.5 Hz, 2H), 7.52-7.38 (m, 6H), 7.01 (dd, J=4.5, 1.0 Hz, 1H), 6.11 (dd, J=4.5, 1.0 Hz, 1H), 5.97 (s, 1H), 5.16 (s, 2H), 4.60-4.53 (m, 2H), 3.78-3.70 (m, 2H), 3.70 (s, 3H), 3.40-3.28 (m, 1H), 3.18-2.98 (m, 2H), 1.44-1.39 (m, 6H); ESI MS m/z 428 [M+H]+; HPLC (Method A) 95.7% (AUC), tR=15.1 min.

Workup

  1. temperatureThe resulting mixture was cooled
  2. filtrationthe precipitate was filtered off
  3. concentrationThe mother liquor was concentrated under vacuum
  4. customThe residue was purified by preparatory TLC (silica gel, 10:1:0.1 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-50569bcfad4c47f3a93863ab22a230c3
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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