Acetic Acid → 4-{2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

HRID 2401117

Reaktionsgleichung

Reaktionsgleichung von HRID 2401117
[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)[N:3]=1.[CH3:20][O:21][C:22]([C:24]1([CH2:30][CH:31]=O)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[O:23].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH3:20][O:21][C:22]([C:24]1([CH2:30][CH2:31][NH:8][C:7]2[C:2]([CH3:1])=[N:3][C:4]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:18][CH2:17][CH2:16][C@@H:15]4[CH3:19])[CH2:10]3)=[CH:5][CH:6]=2)[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1)=[O:23]

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 58468045methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylateHCID 674804612-methyl-6-[(3R)-3-[(2S)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]pyridin-3-amine

Produkt 1

HCID 712803374-{2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl esterAusbeute 97,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2-Methyl-6-((2S,3′R)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamine (58 mg, 0.22 mmol) was dissolved in DCE (1 mL). To this solution was transferred a solution of 4-(2-oxo-ethyl)tetrahydro-pyran-4-carboxylic acid methyl ester (40 mg, 0.22 mmol) in DCE (1 mL). To this clear solution was then added acetic acid (38 μL, 0.66 mmol), followed by addition of powdered NaBH(OAc)3 (140 mg, 0.66 mmol) in one portion under N2 at rt. The yellowish milky solution was stirred at rt. overnight. The reaction was diluted with DCM (40 mL) and quenched with 30 mL of concentrated NH4OH in 70 mL of water. The two layers were separated, and the aqueous layer was extracted with DCM (10 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL), dried (anhydrous potassium carbonate), filtered, and concentrated obtain 92 mg of a crude solid, which was used in the next step of the reaction without purification.

Aufarbeitung

  1. customovernight
  2. customquenched with 30 mL of concentrated NH4OH in 70 mL of water
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (10 mL×2)
  5. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1a2e81ffc99940c6853a71502780ab95
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796278B2

Verknüpfte Notizen

Wird geladen…