Ammonium Chloride → {2-[6-(1-[(1,1-Dimethylethyl)(dimethyl)silyl]-1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazol-5-yl}methanol

HRID 2042376Notes

Reaction equation

HRID 2042376 reaction equation
[CH3:1][C:2]([Si:5]([CH3:44])([CH3:43])[N:6]1[C:14]2[C:9](=[C:10]([C:15]3[CH:23]=[C:22]4[C:18]([CH:19]=[N:20][N:21]4[S:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)(=[O:26])=[O:25])=[C:17]([C:33]4[O:34][C:35]([C:38](OCC)=[O:39])=[CH:36][N:37]=4)[CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)([CH3:4])[CH3:3].ClC1C=C2C(C=NN2S(C2C=CC=CC=2)(=O)=O)=C(C2OC(C(OCC)=O)=CN=2)C=1.[H-].C([Al+]CC(C)C)C(C)C.[Cl-].[NH4+]>ClCCl>[CH3:4][C:2]([Si:5]([CH3:44])([CH3:43])[N:6]1[C:14]2[C:9](=[C:10]([C:15]3[CH:23]=[C:22]4[C:18]([CH:19]=[N:20][N:21]4[S:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)(=[O:26])=[O:25])=[C:17]([C:33]4[O:34][C:35]([CH2:38][OH:39])=[CH:36][N:37]=4)[CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)([CH3:1])[CH3:3]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 59564707Ethyl 2-[6-{1-[(1,1-dimethylethyl)(dimethyl)silyl]-1H-indol-4-yl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazole-5-carboxylateHCID 59564714HCID 59564714, compound

Product 1

HCID 59564700{2-[6-(1-[(1,1-Dimethylethyl)(dimethyl)silyl]-1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazol-5-yl}methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of ethyl 2-[6-{1-[(1,1-dimethylethyl)(dimethyl)silyl]-1H-indol-4-yl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazole-5-carboxylate (containing an impurity consistent with ethyl 2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazole-5-carboxylate)(0.84 g) in dichloromethane (10 ml) at −20° C. was added diisobutylaluminium hydride (2.68 ml, 2.68 mmol, 1M in hexanes). The reaction mixture was stirred at −20° C. for 2 h then 10% ammonium chloride solution (10 ml) added. The mixture was stirred for 5 min then extracted with dichloromethane (10 ml), the layers separated (hydrophobic frit) and the organic purified by silica gel chromatography, eluting with a gradient of cyclohexane and ethyl acetate. The desired fractions were concentrated to give the title compound as a pale yellow solid (0.36 g), which by LCMS contained an impurity consistent with 2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazol-5-yl}methanol.

Workup

  1. stirringThe mixture was stirred for 5 min
  2. extractionthen extracted with dichloromethane (10 ml)
  3. customthe layers separated (hydrophobic frit)
  4. customthe organic purified by silica gel chromatography
  5. washeluting with a gradient of cyclohexane and ethyl acetate
  6. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-902faefc1a1142e49aaf795c39ce52a5
Source dataset
uspto-grants-2013_11
Patent number
US08586583B2

Reaction notes

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