Isopropanol → HCID 46241608, compound

HRID 2096152Notes

Reaction equation

HRID 2096152 reaction equation
[H-].[Na+].[CH3:3][CH:4]([OH:6])[CH3:5].F[C:8]1[N:13]=[CH:12][C:11]([C:14]2([OH:41])[CH2:19][CH2:18][CH:17]([N:20]3[CH2:23][CH:22]([NH:24][C:25]([CH2:27][NH:28][C:29](=[O:40])[C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=4)=[O:26])[CH2:21]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1>CN(C=O)C>[OH:41][C:14]1([C:11]2[CH:12]=[N:13][C:8]([O:6][CH:4]([CH3:5])[CH3:3])=[CH:9][CH:10]=2)[CH2:15][CH2:16][CH:17]([N:20]2[CH2:23][CH:22]([NH:24][C:25]([CH2:27][NH:28][C:29](=[O:40])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:37])[F:38])[CH:31]=3)=[O:26])[CH2:21]2)[CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 46241719HCID 46241719, compound

Product 1

HCID 46241608HCID 46241608, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

NaH (95%, 51 mg, 2 mmol) was added into IPA (4 mL) at 0° C. slowly until bubble disappeared. To this solution was added N-({1-[4-(6-fluoro-pyridin-3-yl)-4-hydroxy-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide (6a, 200 mg, 0.40 mmol) in DMF (1 mL). After addition, the reaction was heated for another 2 hours at 80° C. The reaction solution was quenched with MeOH and partitioned between DCM and water. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compound as a white solid.

Workup

  1. customuntil bubble
  2. additionAfter addition
  3. customThe reaction solution was quenched with MeOH
  4. custompartitioned between DCM and water
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1
  7. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product, which
  11. customwas then purified by a CombiFlash® system

Sources & evidence

ORD record
ord-8cf20e4b1c3d48739e5cc79ce4787d2c
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

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