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 1055110ノート

反応式

HRID 1055110 の反応式
[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]

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-785a92b415aa4c7b9d3980f7418f5368
出典データセット
uspto-grants-2016_07
特許番号
US09394302B2

反応ノート

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