Methanol → N-({1-[4-(6-Cyanoamino-pyridin-2-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2388315Notes

Reaction equation

HRID 2388315 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:17][CH:16]([NH:18][C:19]([CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=4)=[O:20])[CH2:15]3)[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[C:38]#[N:39].CO>CN(C=O)C>[C:38]([NH:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:9][CH2:10][CH:11]([N:14]3[CH2:17][CH:16]([NH:18][C:19]([CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:33])[F:31])[CH:25]=4)=[O:20])[CH2:15]3)[CH2:12][CH2:13]2)[CH:5]=[CH:4][CH:3]=1)#[N:39]

Participants

6

Reactant 4

HCID 887MethanolHCID 10476Cyanogen BromideHCID 24758Sodium hydrideHCID 46945437N-({1-[4-(6-Amino-pyridin-2-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Product 1

HCID 46945440N-({1-[4-(6-Cyanoamino-pyridin-2-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-({1-[4-(6-amino-pyridin-2-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide (120 mg, 0.25 mmol) in DMF (2 mL) was treated with NaH (95%, 10 mg, 0.40 mmol) at 0° C. The reaction was stirred for 20 min. and BrCN (Aldrich, 32 mg, 0.30 mmol) was slowly added. The reaction was warmed to room temperature over 2 hours. MeOH (˜0.2 mL) was added to quenched extra NaH. The reaction solution was partitioned between DCM and water. The aqueous layer was extracted with a chloroform/IPA “cocktail” (3:1 v/v). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a yellow oil, which was purified by silica gel column on 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 white solid.

Workup

  1. customto quenched extra NaH
  2. customThe reaction solution was partitioned between DCM and water
  3. extractionThe aqueous layer was extracted with a chloroform/IPA “cocktail” (3:1 v/v)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil, which
  9. customwas purified by silica gel column on a CombiFlash® system

Sources & evidence

ORD record
ord-1dd2ad133b68460eb97c2752361ba536
Source dataset
uspto-grants-2012_09
Patent number
US08269015B2

Reaction notes

Loading…