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 2171905노트

반응식

HRID 2171905 반응식
[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]

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e1896160a2f34c399baaba16ec37a072
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051319B2

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