Diisobutylaluminum hydride → HCID 71736953, compound

HRID 1483007Notes

Reaction equation

HRID 1483007 reaction equation
[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[C:13]([CH3:20])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:21]3[CH:27]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[C:25]([C:32](OC)=[O:33])=[CH:24][C:22]=3[N:23]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:19])([F:17])[F:18])[C:13]([CH3:20])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:21]3[CH:27]=[C:26]([S:28]([CH3:31])(=[O:29])=[O:30])[C:25]([CH2:32][OH:33])=[CH:24][C:22]=3[N:23]=[C:5]12)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 89815922HCID 89815922, compound

Product 1

HCID 71736953HCID 71736953, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of (R)-methyl 1-isopropyl-2-(5-methyl-4-(trifluoromethyl)pyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (3.5 mg, 0.007 mmol) in dry toluene (3 mL) was cooled to −78° C. A solution of DIBAL-H in toluene (1M, 35 μL, 5 equiv.) was added. The mixture was stirred for 3 h. LC-MS indicated the reaction was complete. The mixture was quenched by sat. NH4Cl solution (200 μL) and methanol (200 μL), before being warmed to r.t. After concentration, the residue was filtered and purified by Gilson to afford 1.53 mg (R)-(1-isopropyl-2-(5-methyl-4-(trifluoromethyl)pyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methanol (46% yield). LC-MS: m/z 484.3 [M+H]+. 1H NMR (CD3OD, 400 MHz): δ 8.52 (s, 1H), 8.27 (s, 1H), 7.99 (s, 1H), 6.05 (d, J=8.0 Hz, 1H), 5.30 (dd, J=14.4 Hz, 4.8 Hz, 1H), 5.12 (s, 2H), 4.51 (dd, J=12.0 Hz, 3.2 Hz, 1H), 4.22 (td, 12.0 Hz, 5.2 Hz, 1H), 3.88 (m, 1H), 3.26 (s, 1H), 2.57 (m, 1H), 2.29 (s, 3H), 1.27 (d, 6.4 Hz, 3H), 1.06 (d, 6.4 Hz, 3H).

Workup

  1. customThe mixture was quenched by sat. NH4Cl solution (200 μL) and methanol (200 μL)
  2. concentrationAfter concentration
  3. filtrationthe residue was filtered
  4. custompurified by Gilson

Sources & evidence

ORD record
ord-b34e9e19e33543dab8592fb0e7d5b46e
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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