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 1483001Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1483001
[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

Komponenten

5

Edukt 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

Produkt 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)methanolAusbeute 12,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-3e44bebbcd794c06b3bced7b437277ef
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09416135B2

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