Sodium Methoxide → (R)-methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

HRID 2171905Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2171905
[C:1]([C:3]1[CH:4]=[C:5]([F:43])[C:6]([NH:29][CH:30]([C:37]2([CH3:42])[CH2:41][CH2:40][CH2:39][CH2:38]2)[CH2:31][C:32]([O:34][CH2:35]C)=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[N:11](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1)#[N:2].C(C1C=C(F)C(N[C@@H](C2(C)CCCC2)CC(OCC)=O)=NC=1C1C2C(=NC=C(F)C=2)N(S(C2C=CC(C)=CC=2)(=O)=O)C=1)#N.C[O-].[Na+]>C1COCC1.C([O-])(O)=O.[Na+].CCOC(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([F:43])[C:6]([NH:29][C@@H:30]([C:37]2([CH3:42])[CH2:38][CH2:39][CH2:40][CH2:41]2)[CH2:31][C:32]([O:34][CH3:35])=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[NH:11][CH:10]=1)#[N:2]

Komponenten

7

Edukt 3

HCID 10942334Sodium MethoxideHCID 71247912racemic ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoateHCID 86714768(R)-ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

Produkt 1

HCID 71247738(R)-methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

To a solution of racemic ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate, 144a, (0.150 g, 0.247 mmol) in THF (20 mL) was added sodium methoxide (0.053 mL of 25% wt solution in MeOH, 0.247 mmol). The reaction mixture was stirred at room temperature for 5 minutes. The reaction mixture was diluted with aqueous saturated NaHCO3 solution and EtOAc. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The product was purified by silica gel chromatography (40% EtOAc/Hexanes) to afford 90 mg of the desired product as a mixture of ethyl and methyl esters. The mixture was taken onto the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 10.18 (s, 1H), 8.65 (dd, J=9.6, 2.5 Hz, 1H), 8.48 (d, J=2.8 Hz, 1H), 8.32 (s, 1H), 7.37 (t, J=14.1 Hz, 1H), 5.38 (d, J=7.9 Hz, 1H), 5.02 (td, J=9.8, 3.5 Hz, 1H), 3.54 (s, 3H), 2.80 (dt, J=15.8, 7.9 Hz, 1H), 2.57 (dd, J=14.9, 9.8 Hz, 1H), 1.80-1.57 (m, 7H), 1.43 (ddd, J=24.5, 14.1, 6.0 Hz, 3H), 1.08 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.60 minutes (M+H) 440.26.

Aufarbeitung

  1. dry with materialThe organic phase was dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe product was purified by silica gel chromatography (40% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e1896160a2f34c399baaba16ec37a072
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051319B2

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