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

HRID 1521537Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1521537
[CH:1]1([C:4]2[C:9]([C:10](OC)=[O:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([C:31](OC)=[O:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C(Cl)Cl.C1(C)C=CC=CC=1>[CH:1]1([C:4]2[C:9]([CH2:10][OH:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([CH2:31][OH:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:2][CH2:3]1.[CH:1]1([C:4]2[C:9]([CH2:10][OH:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([CH2:31][OH:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:2][CH2:3]1

Komponenten

7

Edukt 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89816093(R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Produkt 2

HCID 71736793(R)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanolAusbeute 24,5 %HCID 71736794(S)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanolAusbeute 15,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of (R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (50 mg, 0.1 mmol) in CH2Cl2 (2 mL) was added DIBAL H (1M in toluene, 1 mL, 1 mmol) at −78° C. The mixture was stirred at −78° C. for 1 h and then rt for 1 h. Sat. NH4Cl solution (5 mL) was added slowly at 0° C. and the mixture was filtered. The aqueous layer was extracted with EtOAc (3×5 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 and then SFC separation to afford (R)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol (11.50 mg, 24.5% yield, isomer 1) as a colorless oil and (S)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol (7.10 mg, 15.1% yield, isomer 2) as a colorless oil.

Aufarbeitung

  1. waitrt for 1 h
  2. filtrationthe mixture was filtered
  3. extractionThe aqueous layer was extracted with EtOAc (3×5 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
  9. customSFC separation

Quellen und Nachweise

ORD-Eintrag
ord-2b3295412d4143f29c4eaf28cab1255e
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073931B2

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