Sodium hydride → HCID 178488608, compound

HRID 75502Notes

Reaction equation

HRID 75502 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11]([CH3:14])[CH:10]=2)=[CH:5][CH:4]=1.[H-].[Na+].[Cl:17][C:18]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:19]=1[C:20]([NH:22][C@H:23]1[CH2:28][CH2:27][C@H:26]([CH2:29]OS(C)(=O)=O)[CH2:25][CH2:24]1)=[O:21]>CN(C=O)C.CCOC(C)=O.O>[Cl:17][C:18]1[CH:38]=[CH:37][C:36]([C:39]([F:40])([F:41])[F:42])=[CH:35][C:19]=1[C:20]([NH:22][C@H:23]1[CH2:28][CH2:27][C@H:26]([CH2:29][N:12]2[C:11]([CH3:14])=[CH:10][C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[N:13]2)[CH2:25][CH2:24]1)=[O:21]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 178488614HCID 178488614, compoundHCID 178505299HCID 178505299, compound2×

Product 1

HCID 178488608HCID 178488608, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

5-(4-Methoxyphenyl)-3-methyl-1H-pyrazole (91 mg, 0.483 mmol) was dissolved in dry DMF (2 ml). The flask was flushed with N2 and the solution was treated with NaH (BO % in mineral oil) (19.33 mg, 0.483 mmol) and stirred at RT for ˜10 mins. Trans-methanesulfonic acid 4-(2-chloro-5-trifluoromethyl-benzoylamino)-cyclohexylmethyl ester (Intermediate G) (100 mg, 0.242 mmol) was added and the mixture was heated to 50° C. for 4 hours. After cooling to RT, the mixture was diluted with EtOAc/H2O (20 ml) and transferred to a separating funnel. The organic layer was separated and washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil. Purification of the crude product by chromatography on silica eluting with EtOAc/iso-Hexane afforded the title compound as a white solid; LCMS Rt=1.39 min, [M+H]+ 506.3; Method 2 minLC—30_v002. 1H NMR (400 MHz, CDCl3) δ 7.9 (1H, s), 7.7 (1H, d), 7.6 (1H, d), 7.55 (1H, d), 6.95 (2H, d), 6.25 (1H, s), 5.95 (1H, d), 4.0 (1H, m), 3.95 (2H, d), 3.85 (3H, s), 2.3 (3H, s), 2.2 (2H, d), 2.1 (1H, m), 1.8 (2H, d), 1.25 (4H, m).

Workup

  1. customThe flask was flushed with N2
  2. temperaturethe mixture was heated to 50° C. for 4 hours
  3. temperatureAfter cooling to RT
  4. customtransferred to a separating funnel
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customPurification of the crude product by chromatography on silica eluting with EtOAc/iso-Hexane

Sources & evidence

ORD record
ord-a73cf67f311f4e7daf22b4f6d29938ef
Source dataset
uspto-grants-2014_09
Patent number
US08835444B2

Reaction notes

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