Sodium hydride → 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-3-tetrahydropyran-4-yl-propan-1-one

HRID 710666Notes

Reaction equation

HRID 710666 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH2:18][N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[N:20]4)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.I[CH2:31][CH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH:18]([N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:27])([F:26])[F:28])=[N:20]4)[CH2:31][CH:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27955074-(Iodomethyl)oxaneHCID 733351261-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone

Product 1

HCID 730569281-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-3-tetrahydropyran-4-yl-propan-1-oneYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (0.100 g, 0.25 mmol), 4-(iodomethyl)tetrahydro-2H-pyran (0.165 g, 0.75 mmol) and NaH (0.030 g, 0.75 mmol, 60% in mineral oil) in DMF (0.8 mL) was stirred at rt for 1.5 hrs. It was then quenched with sat. NH4Cl. The mixture was partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo, and purified by reverse phase HPLC to afford the desired product (0.007 g, 6%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.43 (dd, J=8.8, 4.8 Hz, 2H), 7.16 (dd, J=8.8, 8.4 Hz, 2H), 6.31 (s, 1H), 5.54 (m, 1H), 3.95 (m, 2H), 3.78 (m, 1H), 3.47 (m, 1H), 3.34 (m, 2H), 2.75 (m, 2H), 2.30 (s, 3H), 2.20 (m, 3H), 1.88 (m, 3H), 1.40 (m, 3H); MS: (ES) m/z calculated for C25H27F4N5O2 [M+H]+ 506.2, found 506.2.

Workup

  1. customIt was then quenched with sat. NH4Cl
  2. customThe mixture was partitioned between EtOAc (50 mL) and brine (30 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-eaeeb72529b4406da9a0a64f1800bd22
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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