(Diethylamino)sulfur trifluoride → HCID 178461110, compound

HRID 81230Notes

Reaction equation

HRID 81230 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:27][C@H:28]4[CH2:33][CH2:32][C@H:31]([CH3:34])[CH2:30][CH2:29]4)[C:15]([C:17]([C:20]4[C:25]([F:26])=[CH:24][CH:23]=[CH:22][N:21]=4)(O)[CH3:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:35]#[N:36])[N:9]=2)[CH:5]=[N:6][CH:7]=1.CCN(S(F)(F)[F:43])CC>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:27][C@H:28]4[CH2:33][CH2:32][C@H:31]([CH3:34])[CH2:30][CH2:29]4)[C:15]([C:17]([F:43])([C:20]4[C:25]([F:26])=[CH:24][CH:23]=[CH:22][N:21]=4)[CH3:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:35]#[N:36])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 178467409HCID 178467409, compound

Product 1

HCID 178461110HCID 178461110, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-2-[(1RS)-1-(3-fluoropyridin-2-yl)-1-hydroxyethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (156 mg, 0.31 mmol) in CH2Cl2 (10.0 mL) at −40° C. under a nitrogen atmosphere was added DAST (0.08 mL, 0.22 mmol), and the resulting solution was stirred at this temperature for 1 hour. The reaction mixture was then quenched with a saturated aqueous solution of NaHCO3 (5 mL) and extracted with CH2Cl2 (2×15 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the resulting residue on a silica gel column (0 to 100% ethyl acetate/hexanes) afforded 4-(5-chloropyridin-3-yl)-2-[(1RS)-1-fluoro-1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS APCl calcd. for C27H25ClF2N6 [M+H]+ 507. found 507. The two enantiomers were separated on a chiralpak-AD column (15% IPA/heptane) to afford faster eluting Enantiomer A and slower eluting Enantiomer B.

Workup

  1. customThe reaction mixture was then quenched with a saturated aqueous solution of NaHCO3 (5 mL)
  2. extractionextracted with CH2Cl2 (2×15 mL)
  3. washThe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the resulting residue on a silica gel column (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-796693684dfb49a3b32f0bc75f15ea06
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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