HCID 86722465, compound → HCID 86722467, compound

HRID 718853Notes

Reaction equation

HRID 718853 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20](=[O:29])/[C:21](=[CH:22]/[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)/[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1>C1(C)C=CC=CC=1.[OH-].[OH-].[Pd+2]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20](=[O:29])[CH:21]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 86722465HCID 86722465, compound

Product 1

HCID 86722467HCID 86722467, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 1140TolueneSolvent

Procedure

(E)-1-(4-Fluorophenyl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one (19.53 g, 50.8 mmol) (assumed 100% for previous reaction), in toluene (500 mL) with palladium hydroxide on carbon (20% wet) (1.784 g, 2.54 mmol) was stirred for about 22 h under an atmosphere of hydrogen provided by a balloon. The catalyst was removed by filtration through a pad of Celite® and the pad was washed with DCM (250 mL). The filtrate was concentrated under reduced pressure then the material was purified on silica gel (330 g) using a gradient from 0-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield 1-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one (115, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (16.47 g, 84%); LC/MS, method 3, Rt=1.97 min, MS m/z 387 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.47-8.46 (m, 1H), 8.34 (s, 1H), 8.33-8.26 (m, 2H), 8.09 (s, 1H), 7.72-7.68 (m, 1H), 7.46-7.34 (m, 3H), 7.23-7.17 (m, 1H), 5.00-4.97 (m, 1H), 3.88-3.82 (m, 1H), 3.72-3.65 (m, 1H), 3.36-3.29 (m, 1H), 3.25-3.19 (m, 1H), 3.07-2.99 (m, 1H), 2.54-2.48 (m, 1H), 2.33-2.25 (m, 1H), 1.80-1.69 (m, 1H).

Workup

  1. customprovided by a balloon
  2. customThe catalyst was removed by filtration through a pad of Celite®
  3. washthe pad was washed with DCM (250 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe material was purified on silica gel (330 g)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc312141a7114e77beb73cb4ae5daf7f
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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