Diisobutylaluminum hydride → HCID 71736791, compound

HRID 1482998Notes

Reaction equation

HRID 1482998 reaction equation
[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([O:16][CH3:17])[C:13]([C:18]([F:21])([F:20])[F:19])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:22]3[CH:28]=[C:27]([S:29]([CH3:32])(=[O:31])=[O:30])[C:26]([C:33](OC)=[O:34])=[CH:25][C:23]=3[N:24]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C(Cl)Cl.C1(C)C=CC=CC=1>[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([O:16][CH3:17])[C:13]([C:18]([F:21])([F:19])[F:20])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:22]3[CH:28]=[C:27]([S:29]([CH3:32])(=[O:30])=[O:31])[C:26]([CH2:33][OH:34])=[CH:25][C:23]=3[N:24]=[C:5]12)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89828105HCID 89828105, compound

Product 1

HCID 71736791HCID 71736791, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-methyl 1-isopropyl-2-(4-methoxy-5-(trifluoromethyl)pyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (15 mg, 0.028 mmol) in CH2Cl2 (2 mL) was added DIBAL H (1M in toluene, 0.1 mL, 0.1 mmol) at −78° C. The mixture was stirred at −78° C. for 2 h and warmed to rt for 6 h. Sat. NH4Cl solution (1 mL) was added and the mixture was filtered. The filtrate was concentrated under vacuum. Water (5 mL) and EtOAc (5 mL) were added to the mixture. The aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC to afford (R)-(1-isopropyl-2-(4-methoxy-5-(trifluoromethyl)pyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methanol (3.50 mg, 24.6% yield) as a white solid. Analytical chiral HPLC: tR=6.598 min in 15 min chromatography, 94.60% ee (Method: OD-H_3_5_40_2.35 ML). LC-MS MS (ESI) m/z 500.1 [M+H]+. 1H NMR (CDCl3 300 MHz): δ 8.31 (s, 1H), 8.12 (s, 1H), 7.86 (s, 1H), 6.02-5.98 (m, 1H), 5.43-5.38 (m, 1H), 5.04-4.98 (m, 2H), 4.32-4.28 (m, 1H), 4.16 (dt, J=5.1 and 12.0 Hz, 1H), 4.01 (s, 3H), 3.77-3.68 (m, 1H), 3.21 (s, 3H), 3.11-3.06 (m, 1H), 2.50-2.47 (m, 1H), 1.30 (d, J=6.6 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H).

Workup

  1. temperaturewarmed to rt for 6 h
  2. filtrationthe mixture was filtered
  3. concentrationThe filtrate was concentrated under vacuum
  4. additionWater (5 mL) and EtOAc (5 mL) were added to the mixture
  5. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-4c6cf8209a6d4528bc735fa462fd0252
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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