Acetic Acid → 3-(1-((1-cyclopropylpiperidin-4-yl)methyl)-1H-pyrazol-4-yl)-6-fluoro-1-(phenylsulfonyl)-1H-indole

HRID 2274822Notes

Reaction equation

HRID 2274822 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:21]=[N:22][N:23]([CH2:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:24]=3)=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.CC(O)=O.C(O[C:39]1(O[Si](C)(C)C)[CH2:41][CH2:40]1)C.[BH3-]C#N.[Na+].[NH4+].[Cl-]>C(Cl)Cl.CO.C1COCC1>[CH:39]1([N:29]2[CH2:30][CH2:31][CH:26]([CH2:25][N:23]3[CH:24]=[C:20]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([S:11]([C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)(=[O:12])=[O:13])[CH:7]=4)[CH:21]=[N:22]3)[CH2:27][CH2:28]2)[CH2:41][CH2:40]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 1180606356-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-indole2×

Product 1

HCID 1180605763-(1-((1-cyclopropylpiperidin-4-yl)methyl)-1H-pyrazol-4-yl)-6-fluoro-1-(phenylsulfonyl)-1H-indoleYield 45.4%

Reagents, catalysts & solvents 1

HCID 22912779methanol THF dichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-indole (Intermediate 21; 277 mg; 0.63 mmol), HOAc (121 mg; 2.01 mmol), (1-ethoxycyclopropoxy)trimethylsilane (220 mg; 1.26 mmol) and NaBH3CN (60 mg; 0.95 mmol) in DCM/MeOH/THF (10 ml/1 ml/15 ml) was stirred at 70° C. overnight. The reaction mixture was added saturated aqueous NH4Cl (20 mL), extracted with EtOAc (50 mL×2). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and purified by reverse phase flash chromatography to afford 137 mg (45%) of the title compound as a yellow oil.

Workup

  1. extractionextracted with EtOAc (50 mL×2)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by reverse phase flash chromatography

Sources & evidence

ORD record
ord-dc85563626384f76ad6ec3393308525f
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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