Diisobutylaluminum hydride → (R)-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-methylpyrimidin-5-yl)methanol

HRID 1521534Notes

Reaction equation

HRID 1521534 reaction equation
[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([CH3:16])[C:13]([C:17](OC)=[O:18])=[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.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[OH:33][CH2:32][C:25]1[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:27][C:21]2[N:6]3[CH2:7][CH2:8][N:9]([C:10]4[N:15]=[C:14]([CH3:16])[C:13]([CH2:17][OH:18])=[CH:12][N:11]=4)[C@H:4]([CH:1]([CH3:2])[CH3:3])[C:5]3=[N:23][C:22]=2[CH:24]=1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89815891(R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Product 1

HCID 71736792(R)-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-methylpyrimidin-5-yl)methanolYield 12.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (15 mg, 0.03 mmol) in toluene (2 mL) was added DIBAL H (1M in toluene, 0.3 mL, 0.3 mmol) at −78° C. The mixture was stirred at −78° C. for 2 h and then rt for 30 mins. Sat. NH4Cl solution (5 mL) was added slowly at 0° C. and the mixture was filtered. The aqueous layer was extracted with EtOAc (3×10 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)-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-methylpyrimidin-5-yl)methanol (1.6 mg, 12.3% yield) as a colorless oil. LC-MS MS (ESI) m/z 446.2 [M+H]+. 1H NMR (CD3OD 400 MHz): δ 8.26 (s, 1H), 8.23 (s, 1H), 7.99 (s, 1H), 6.00 (d, J=8.8 Hz, 1H), 5.17 (s, 2H), 4.90-4.79 (m, 1H), 4.67 (s, 2H), 4.45-4.44 (m, 1H), 4.25-4.18 (m, 1H), 4.15-4.04 (m, 1H), 3.31 (s, 3H), 2.58-2.49 (m, 1H), 2.45 (s, 3H), 1.25 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.8 Hz, 3H).

Workup

  1. waitrt for 30 mins
  2. filtrationthe mixture was filtered
  3. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-31194249e9364c9b9c206096fd9904ff
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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