Methanol → 2-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol

HRID 1521520Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1521520
C[O:2][C:3]([C:5]1[C:6]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][N:15]([C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:22][N:21]=4)[C@H:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:34]=1)=O.CC(C[AlH]CC(C)C)C.CO>C(Cl)Cl>[OH:2][CH2:3][C:5]1[C:6]([S:35]([CH3:38])(=[O:36])=[O:37])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][N:15]([C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:22][N:21]=4)[CH:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:34]=1

Komponenten

5

Edukt 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 89816015(R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Produkt 1

HCID 781643372-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-olAusbeute 68,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a solution of (R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (109 mg, 0.196 mmol) in DCM (4 mL) was added a solution of DIBAL-H in DCM (0.98 mL of a 1.0 M solution, 0.98 mmol) dropwise at −78° C. The reaction slowly warmed to −10° C. over approximately 1 h, at which point 1 mL of MeOH was added to quench the excess DIBAL-H. Sat. aq. Rochelle salt (potassium sodium tartrate (KNaC4H4O6)) solution (5 mL) and DCM (5 mL) were added and the mixture stirred vigorously for 15 min. The DCM layer was separated and the aqueous layer was extracted with DCM (2×5 mL). The DCM layers were combined, dried using Na2SO4 and evaporated to give the crude product. Purification using ISCO FCC eluting with 70% EtOAc in Hexanes gave 71 mg of 2-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol as a racemic mixture (69%). LC-MS MS (ESI) m/z 528.25 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 8.72 (s, 1H), 8.05 (s, 1H), 7.80 (s, 1H), 6.01 (d, J=7.6 Hz, 1H), 5.27 (d, J=4.4 and 14.0 Hz, 1H), 5.00-4.86 (m, 2H), 4.26-4.08 (m, 2H), 3.74-3.67 (m, 1H), 3.15 (s, 3H), 3.15-3.10 (m, 1H), 2.47-2.40 (m, 1H), 1.96 (b, 1H), 1.59 (s, 6H), 1.23 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.8 Hz, 3H).

Aufarbeitung

  1. customThe reaction
  2. additionwas added
  3. customto quench the excess DIBAL-H
  4. additionSat. aq. Rochelle salt (potassium sodium tartrate (KNaC4H4O6)) solution (5 mL) and DCM (5 mL) were added
  5. customThe DCM layer was separated
  6. extractionthe aqueous layer was extracted with DCM (2×5 mL)
  7. customdried
  8. customevaporated
  9. customto give the crude product
  10. customPurification
  11. washeluting with 70% EtOAc in Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-7f0ef2e4352d4be684d4ee27bc9d51dc
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073931B2

Notizen zur Reaktion

Wird geladen…