Triethylamine → 5-[1-(2-Hydroxyethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60332Notes

Reaction equation

HRID 60332 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:29]#[N:30])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:31]=[CH:32][CH:33]=[N:34][C:11]2=3)(=O)=O)C=CC=CC=1.C(N(CC)CC)C>CO>[OH:28][CH2:27][CH2:26][N:23]1[CH2:22][CH2:21][CH:20]([O:19][C:18]2[C:13]3[C:12]4[CH:31]=[CH:32][CH:33]=[N:34][C:11]=4[NH:10][C:14]=3[CH:15]=[N:16][C:17]=2[C:29]#[N:30])[CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 67248027HCID 67248027, compound

Product 1

HCID 532515305-[1-(2-Hydroxyethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 45.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 9-benzenesulfonyl-5-[1-(2-hydroxyethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (125 mg, 0.26 mmol) and triethylamine (1 mL) in methanol (10 mL) was heated to 60° C. for 3 hours. The mixture was concentrated in-vacuo and the resultant residue purified by flash chromatography (silica, 10 g column, ISCO, 0-8% methanol in dichloromethane). The resultant material was triturated with acetonitrile and methanol to afford the title compound as an off-white solid (40 mg, 45%). LCMS (Method C): RT=4.83 min, M+H+=338.2. 1H NMR (400 MHz, DMSO-d6): 8.79 (s, 1H), 8.70 (dd, J=4.8, 1.6 Hz, 1H), 8.59 (dd, J=7.9, 1.7 Hz, 1H), 7.47 (dd, J=7.9, 4.8 Hz, 1H), 4.71-4.69 (m, 1H), 4.38 (s, 1H), 3.49 (s, 2H), 2.93-2.81 (m, 2H), 2.40 (t, J=6.3 Hz, 2H), 2.15 (t, J=11.1 Hz, 2H), 2.06 (d, J=12.0 Hz, 2H), 1.93-1.92 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated in-vacuo
  2. customthe resultant residue purified by flash chromatography (silica, 10 g column, ISCO, 0-8% methanol in dichloromethane)
  3. customThe resultant material was triturated with acetonitrile and methanol

Sources & evidence

ORD record
ord-45c786810f0d45589df66848202b9e64
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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