Diisobutylaluminum hydride → HCID 71737122, compound

HRID 1483011Notes

Reaction equation

HRID 1483011 reaction equation
[CH:1]([CH:4]1[C:9]2=[CH:10][C:11]3[CH:12]=[CH:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6][N:5]1[C:21]1[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[C:24]([C:31]([O-])=[O:32])=[CH:23][N:22]=1)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C>ClCCl>[CH:1]([C@@H:4]1[C:9]2=[CH:10][C:11]3[CH:12]=[CH:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6][N:5]1[C:21]1[N:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[C:24]([CH2:31][OH:32])=[CH:23][N:22]=1)([CH3:3])[CH3:2].[CH:1]([C@H:4]1[C:9]2=[CH:10][C:11]3[CH:12]=[CH:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6][N:5]1[C:21]1[N:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[C:24]([CH2:31][OH:32])=[CH:23][N:22]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 131733109HCID 131733109, compound

Product 2

HCID 71737122HCID 71737122, compoundYield 7.84%HCID 71737123HCID 71737123, compoundYield 6.97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate (25 mg, 0.05 mmol) in dichloromethane (1 mL) was added DIBAL-H (0.25 mg, 0.25 mmol, 1M in toluene) at −78° C. under nitrogen. The reaction mixture was stirred at −78° C. for 1 h. The reaction was quenched with sat. NH4Cl (5 mL) at −78° C. and then extracted with dichloromethane (30 mL×3). The combined organic layers were concentrated, purified by preparative TLC on silica gel eluting with PE/EtOAc 1:1 and then by SFC separation to afford (R)-(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol (1.80 mg, 7.84% yield, isomer 1) as a colorless oil and (S)-(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol (1.60 mg, 6.97% yield, isomer 2) as a colorless oil.

Workup

  1. customThe reaction was quenched with sat. NH4Cl (5 mL) at −78° C.
  2. extractionextracted with dichloromethane (30 mL×3)
  3. concentrationThe combined organic layers were concentrated
  4. custompurified by preparative TLC on silica gel eluting with PE/EtOAc 1:1
  5. customby SFC separation

Sources & evidence

ORD record
ord-eef6732b623d4b2abf3ebbdaab93f679
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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