Potassium Phosphate, Tribasic → HCID 58266416, compound

HRID 1888512Notes

Reaction equation

HRID 1888512 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=3[C:12]3[CH:22]=[C:23]([C:26]4[CH:31]=[CH:30][C:29]([CH2:32][N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[CH:28][CH:27]=4)[CH:24]=[N:25][C:11]2=3)(=O)=O)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[OH-].[K+].CO.O>[OH:19][C:18]1[C:13]2[C:12]3[CH:22]=[C:23]([C:26]4[CH:31]=[CH:30][C:29]([CH2:32][N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[CH:28][CH:27]=4)[CH:24]=[N:25][C:11]=3[NH:10][C:14]=2[CH:15]=[N:16][C:17]=1[C:20]#[N:21]

Participants

6

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 58266539HCID 58266539, compound

Product 1

HCID 58266416HCID 58266416, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 14797Potassium HydroxideSolvent

Procedure

9-Benzenesulfonyl-5-hydroxy-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (50 mg, 0.01 mmol) was dissolved in 0.15N potassium hydroxide solution in methanol (7 mL). The reaction mixture was stirred for 2.5 h then treated with a solution of monobasic potassium phosphate (136 mg, 1.0 mmol) in water (2 mL). The resultant mixture was concentrated in vacuo and the resultant residue was diluted with water (5 mL). The pH of the aqueous phase was adjusted to 7 by the addition of 1N hydrochloric acid. The aqueous phase was extracted with ethyl acetate, DCM and THF. The combined organic phase was concentrated in vacuo and the residue purified by flash chromatography (silica, 500 mg column, Si-SPE, 10-20% methanol in DCM) to afford the title compound as its hydrochloride salt (25 mg, 63%). 1H NMR (DMSO-D6, 400 MHz): 12.91 (s, 1H), 11.86 (br. s, 1H), 10.41 (s, 1H), 9.13 (d, J=2.2 Hz, 1H), 9.00 (d, J=2.2 Hz, 1H), 8.60 (s, 1H), 7.93 (d, J=8.1 Hz, 2H), 7.76 (d, J=8.1 Hz, 2H), 4.33 (d, J=5.2 Hz, 2H), 3.39-3.29 (m, 2H), 2.92-2.83 (m, 2H), 1.85-1.63 (m, 5H), 1.45-1.31 (m, 1H). LCMS (Method A): RT=5.32 min, M+H+=384.

Workup

  1. concentrationThe resultant mixture was concentrated in vacuo
  2. additionthe resultant residue was diluted with water (5 mL)
  3. additionThe pH of the aqueous phase was adjusted to 7 by the addition of 1N hydrochloric acid
  4. extractionThe aqueous phase was extracted with ethyl acetate, DCM and THF
  5. concentrationThe combined organic phase was concentrated in vacuo
  6. customthe residue purified by flash chromatography (silica, 500 mg column, Si-SPE, 10-20% methanol in DCM)

Sources & evidence

ORD record
ord-1581b99838cf4e518f5cb67582d40383
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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