Diisobutylaluminumhydride → HCID 11691433, compound

HRID 1444112Notes

Reaction equation

HRID 1444112 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-3aee1c835af546dabac6e6abd9827c5d
Source dataset
uspto-grants-2010_02
Patent number
US07662830B2

Reaction notes

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