Diisobutylaluminumhydride → (5-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)pyrimidin-4-yl]-piperazin-1-yl}-pyridin-3-yl)-methanol

HRID 2195038Notes

Reaction equation

C([O:3][C:4](=O)[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[N:21]=[C:20]([N:31]4[CH2:35][CH2:34][CH2:33][CH:32]4[CH3:36])[N:19]=3)[CH2:14][CH2:13]2)=[N:7][CH:6]=1)C.[H-].C([Al+]CC(C)C)C(C)C>C(Cl)Cl>[Cl:11][C:9]1[CH:10]=[C:5]([CH2:4][OH:3])[CH:6]=[N:7][C:8]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[N:21]=[C:20]([N:31]3[CH2:35][CH2:34][CH2:33][CH:32]3[CH3:36])[N:19]=2)[CH2:14][CH2:13]1

Participants

Conditions

Temperature: -78 °C

Procedure

Dissolve 5-chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-nicotinic acid ethyl ester (595 mg, 1.13 mmol, prepared in Example 1-B, step 5, above) in DCM and cool to −78° C. using a dry ice/acetone bath. Add diisobutylaluminum hydride (4.53 mL, 1N in hexanes) dropwise and continue stirring for 1 h at −78° C. Add excess Na2SO4.10H2O, stir at −78° C. for 5 min and then remove the cooling bath and allow to come to room temperature. Filter the mixture through celite washing with DCM then concentrate under reduced pressure. The resulting oil is purified using flash chromatography (30-50% EtOAc/hexanes eluent) to afford the title compound as a white foam.

Workup

customremove the cooling bath
customto come to room temperature
filtrationFilter the mixture
washthrough celite washing with DCM
concentrationthen concentrate under reduced pressure
customThe resulting oil is purified

Sources & evidence

ORD record: ord-bceddd916c3f4e21a42a87e036f8c09d
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08334382B2

Reaction notes

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