Piperidine → HCID 72550730, compound

HRID 920646Notes

Reaction equation

HRID 920646 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21]([C:23]5[S:24][CH:25]=[CH:26][N:27]=5)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:28]([C:31]2[CH:32]=[N:33][CH:34]=[C:35](F)[CH:36]=2)(=[O:30])=[O:29])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.[NH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>CN1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21]([C:23]5[S:24][CH:25]=[CH:26][N:27]=5)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:28]([C:31]2[CH:32]=[N:33][CH:34]=[C:35]([N:38]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]3)[CH:36]=2)(=[O:30])=[O:29])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 72550507HCID 72550507, compound

Product 1

HCID 72550730HCID 72550730, compoundYield 31.3%

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-(1-(4-fluorophenyl)-6-((5-fluoropyridin-3-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(thiazol-2-yl)methanone (100 mg, 0.185 mmol) and piperidine (47 mg, 0.56 mmol) in N-methylpyrrolidine (1 mL) was heated at 100° C. for 6 hours. The mixture was cooled and the reaction mixture was purified by preparative HPLC (Gilson, Acidic (0.1% Formic acid), Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 5-95% acetonitrile in water) to give (R)-(1-(4-fluorophenyl)-6-((5-(piperidin-1-yl)pyridin-3-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(thiazol-2-yl)methanone as a white solid (35 mg). LCMS (Method F, ES-API): RT 2.64 min, m+H=605; 1H NMR (400 MHz, CDCl3): δ 8.39 (d, 1H, J=3.0 Hz), 8.27 (d, 1H, J=2.0 Hz), 8.05 (d, 1H, J=3.0 Hz), 7.65 (d, 1H, J=3.0 Hz), 7.54-7.41 (m, 2H), 7.31-7.30 (m, 2H). 7.19-7.14 (m, 2H), 6.53 (d, 1H, J=2.0 Hz), 5.51 (dd, 1H, J=12.0, 2.0 Hz), 4.21 (d, 1H, J=17.0 Hz), 3.90-3.86 (m, 1H), 3.27-3.25 (m, 4H), 2.91-2.81 (m, 3H), 2.61-2.52 (m, 2H), 1.75-1.56 (m, 6H).

Workup

  1. temperatureThe mixture was cooled
  2. customthe reaction mixture was purified by preparative HPLC (Gilson, Acidic (0.1% Formic acid), Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 5-95% acetonitrile in water)

Sources & evidence

ORD record
ord-16e21c08950348d589535e12e255dc10
Source dataset
uspto-grants-2016_03
Patent number
US09273047B2

Reaction notes

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