Potassium Phosphate, Tribasic → (E)-4-(8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-2(5H)-yl)-2-methylbutan-2-ol

HRID 1400559Notes

Reaction equation

HRID 1400559 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][C:17]([CH3:20])([OH:19])[CH3:18])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.Br[CH:22]=[C:23]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH3:24].N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:22]=[C:23](/[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)\[CH3:24])[C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][C:17]([CH3:20])([OH:19])[CH3:18])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 684857494-(8-Chloro-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-y1-)2-methyl butan-2-olHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Product 1

HCID 59455082(E)-4-(8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-2(5H)-yl)-2-methylbutan-2-olYield 65.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

4-(8-Chloro-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl-)2-methyl butan-2-ol (292 mg, 1.0 mmol), 1-((1-bromoprop-1-en-2-yl)-4-fluorobenzene (322 mg, 1.5 mmol), L-proline (23 mg, 0.2 mmol), Cuprous (I) iodide (19 mg, 0.1 mmol), potassium phosphate (636 mg, 3.0 mmol) in DMF (5 mL) were charged in a reaction vessel and nitrogen gas purged into the reaction mixture. The reaction mixture was heated at 95° C. overnight. The reaction was monitored by TLC/LCMS. The reaction mixture was diluted with water (20 mL) and the desired compound extracted with DCM (20 mL×3). The organic layer was dried over sodium sulfate and concentrated under vacuum to obtain the crude compound which was purified by reverse phase HPLC to obtain 280 mg of desired product as the free base. The free base compound was converted to HCl salt by treatment with ethanolic HCl. 1H NMR (CD3OD, HCl salt) δ (ppm): 7.68 (m, 2H), 7.58 (s, 1H), 7.20 (m, 4H), 6.98 (s, 1H), 4.80 (m, 1H), 4.40 (m, 1H), 3.98 (m, 1H), 3.61 (m, 1H), 3.55 (m, 2H), 3.20 (m, 2H), 2.06 (m, 2H), 1.96 (s, 3H), 1.35 (s, 6H).

Workup

  1. customnitrogen gas purged into the reaction mixture
  2. additionThe reaction mixture was diluted with water (20 mL)
  3. extractionthe desired compound extracted with DCM (20 mL×3)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto obtain the crude compound which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-201b9d97b4ef4c87a3de9bfec52dab6f
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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