Diisobutylaluminum hydride → (2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol

HRID 1482978Notes

Reaction equation

HRID 1482978 reaction equation
[CH:1]([CH:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[C:13]([C:20](OCC)=[O:21])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:25]3[CH:31]=[C:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:29]=[CH:28][C:26]=3[N:27]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH:1]([CH:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[C:13]([CH2:20][OH:21])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:25]3[CH:31]=[C:30]([S:32]([CH3:35])(=[O:33])=[O:34])[CH:29]=[CH:28][C:26]=3[N:27]=[C:5]12)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 71735988ethyl 2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate

Product 1

HCID 71735989(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanolYield 63%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate (10 mg, 0.02 mmol, prepared according to example 3) in anhydrous toluene (0.5 mL) was added DIBAL-H (0.2 mL, 0.20 mmol, 1M in THF) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. Sat. NH4Cl (5 mL) at −78° C. was added to the mixture, which was then extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered, concentrated and then purified by basic preparative HPLC to afford a racemic mixture of (2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol (5.80 mg, 63% yield) as a white solid. LC-MS m/z 470.1 [M+H]+. 1H NMR (CDCl3 400 MHz): δ 8.68 (s, 1H), 8.01 (s, 1H), 7.93-7.81 (m, 2H), 6.11 (d, J=8.0 Hz, 1H), 5.38 (dd, J=5.2 Hz, J=14.4 Hz, 1H), 4.74 (s, 2H), 4.38-4.30 (m, 1H), 4.25-4.15 (m, 1H), 3.86-3.76 (m, 1H), 3.10 (s, 3H), 2.56-2.47 (m, 1H), 1.32 (d, J=6.8 Hz, 3H), 1.08 (d, J=6.8 Hz, 3H).

Workup

  1. extractionwas then extracted with EtOAc (3×5 mL)
  2. washThe combined organic layers were washed with brine (5 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by basic preparative HPLC
  7. customto afford

Sources & evidence

ORD record
ord-5780290b2ae848fea0942efb87bd7257
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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