Diisobutylaluminumhydride → HCID 11691433, compound

HRID 2195046Notes

Reaction equation

HRID 2195046 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[C:21]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[N:20]=[C:19]([N:30]4[CH2:34][CH2:33][CH2:32][CH:31]4[CH3:35])[N:18]=3)[C@H:13]([CH3:36])[CH2:12]2)=[N:6][CH:5]=1.[H-].C([Al+]CC(C)C)C(C)C>C(Cl)Cl>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:21]2[N:20]=[C:19]([N:30]3[CH2:34][CH2:33][CH2:32][CH:31]3[CH3:35])[N:18]=[C:17]([N:14]3[CH2:15][CH2:16][N:11]([C:7]4[N:6]=[CH:5][C:4]([CH2:3][OH:2])=[CH:9][C:8]=4[CH3:10])[CH2:12][C@H:13]3[CH3:36])[CH:22]=2)=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 59168330HCID 59168330, compound

Product 1

HCID 11691433HCID 11691433, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve 6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-nicotinic acid methyl ester (78 mg, 0.155 mmol) in DCM and cool to −78° C. using a dry ice/acetone bath. Add diisobutylaluminum hydride (0.619 mL, 1M in hexanes) dropwise and continue stirring for 1 h at −78° C. Add excess Na2SO4.10H2O and 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, and then concentrate under reduced pressure. Purify the resulting oil using flash chromatography (30-50% EtOAc/hexanes eluent) to afford the title compound as a white foam. 1H NMR (400 MHz, CDCl3): δ 1.32 (m, 3H, CH3); 1.40 (m, 3H, CH3); 1.69 (m, 1H, CH2CH2); 1.90 (m, 1H, CH2CH2); 2.05 (m, 2H, CH2CH2); 2.36 (s, 3H, Ar—CH3); 3.00 (m, 1H); 3.08 (m, 1H); 3.37 (m, 2H); 3.48 (m, 1H); 3.68 (m, 2H); 4.34 (m, 2H); 4.69 (s, 2H, CH2OH); 4.71 (m, 1H); 6.24 (s, 1H, Ar—H); 7.10 (m, 2H); 7.48 (d, 1H, J=2.0 Hz); 8.00 (m, 2H); 8.11 (s, 1H).

Workup

  1. customremove the cooling bath
  2. customto come to room temperature
  3. filtrationFilter the mixture
  4. washthrough celite washing with DCM
  5. concentrationconcentrate under reduced pressure
  6. customPurify the resulting oil

Sources & evidence

ORD record
ord-7a4d1e2c94274463a20307a48ce1c7a4
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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