5-Dimethylamino-1-methyl-3-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one → (S)-5-Dimethylamino-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1-methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one

HRID 1371013Notes

Reaction equation

HRID 1371013 reaction equation
[CH3:1][N:2]([CH3:20])[C:3]1[N:8]=[C:7]2[N:9]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:10](=[O:13])[N:11]([CH3:12])[C:6]2=[CH:5][CH:4]=1.[CH3:21][S:22]([N:25]1[CH2:30][CH2:29][C:28]2[N:31]([CH2:44][C@@H:45]3[CH2:47][O:46]3)[N:32]=[C:33]([C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=3)[C:27]=2[CH2:26]1)(=[O:24])=[O:23]>CCO.ClC(Cl)C>[CH3:1][N:2]([CH3:20])[C:3]1[N:8]=[C:7]2[N:9]([CH:14]3[CH2:19][CH2:18][N:17]([CH2:47][C@H:45]([OH:46])[CH2:44][N:31]4[C:28]5[CH2:29][CH2:30][N:25]([S:22]([CH3:21])(=[O:24])=[O:23])[CH2:26][C:27]=5[C:33]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([F:42])([F:43])[F:41])=[CH:36][CH:35]=5)=[N:32]4)[CH2:16][CH2:15]3)[C:10](=[O:13])[N:11]([CH3:12])[C:6]2=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 222938675-Dimethylamino-1-methyl-3-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-oneHCID 53348235(R)-5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 50943347(S)-5-Dimethylamino-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1-methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-oneYield 112.3%

Reagents, catalysts & solvents 1

HCID 18381953Dichloroethane ethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring solution of 0.24 g (0.0009 mol) of 5-dimethylamino-1-methyl-3-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one in EtOH/Dichloroethane (1.5 mL/1.5 mL) was added 0.23 g (0.0005 mol) of (R)-5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. The reaction mixture was heated to 80° C. and stirred for 16 h and concentrated. The crude product was then dissolved in CH2Cl2 (40 mL) and purified using flash chromatography (0-6% MeOH/CH2Cl2) affording 0.38 g (97%) of the desired product as a white solid. MS (electrospray): exact mass calculated for C31H39F3N8O4S, 676.28; m/z found, 677.28 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.71 and 7.67 (A and B of AA′BB′ quartet, Jab=8.3 Hz, 4H), 7.03 (d, J=8.6 Hz, 1H), 6.16 (d, J=8.6 Hz, 1H), 4.58 and 4.56 (A and B of AB quartet, Jab=14.5 Hz, 2H), 4.36 (ft, J=12.1 Hz, 4.04 Hz, 1H), 4.25-4.01 (m, 4H), 3.77-3.60 (m, 2H), 3.33 (s, 3H), 3.16-3.04 (m, 2H), 3.03 (s, 6H), 2.99-2.90 (m, 2H), 2.88 (s, 3H), 2.77 (qd, J=12.1 Hz, 3.54 Hz, 2H), 2.56-2.42 (m, 3H), 2.21 (t, J=11.6 Hz, 1H), 1.75 (d, J=11.6 Hz, 2H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe crude product was then dissolved in CH2Cl2 (40 mL)
  3. custompurified

Sources & evidence

ORD record
ord-898a6155a2c747f2bb299474c9131600
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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