N,N-二异丙基乙胺 → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-amide

HRID 246169笔记

反应方程式

HRID 246169 反应方程式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[NH2:39][C@H:40]([CH2:48][O:49][CH3:50])[C:41]([N:43]1[CH2:46][CH:45]([F:47])[CH2:44]1)=[O:42].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(#N)C>[F:47][CH:45]1[CH2:46][N:43]([C:41](=[O:42])[C@H:40]([NH:39][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[CH:19]=2)=[O:22])[CH2:48][O:49][CH3:50])[CH2:44]1

参与物

6

反应物 4

HCID 81531N,N-二异丙基乙胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280390(R)-2-amino-1-(3-fluoro-azetidin-1-yl)-3-methoxy-propan-1-one trifluoroacetate

产物 1

HCID 712884162-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-amide收率 47.7%

试剂、催化剂与溶剂 1

HCID 6342乙腈溶剂

实验过程

A 10 mL round-bottomed flask was charged with 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (75 mg, 0.16 mmol), (R)-2-amino-1-(3-fluoro-azetidin-1-yl)-3-methoxy-propan-1-one trifluoroacetate (63 mg, 0.21 mmol), and HATU (63 mg, 0.21 mmol). Then added acetonitrile (1 mL) followed by N,N-diisopropylethylamine (0.55 mL, 3.15 mmol). The light yellow reaction mixture was stirred at room temperature overnight then quenched with water. The mixture was extracted with dichloromethane. The organic layers were combined, dried over Na2SO4, and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptanes (gradient: 5-90% EtOAc) to afford 47 mg (47%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-amide as an off-white solid. MS: [M+H]+=616.

后处理

  1. customthen quenched with water
  2. extractionThe mixture was extracted with dichloromethane
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography over SiO2 with EtOAc/heptanes (gradient: 5-90% EtOAc)

来源与证据

ORD记录
ord-311ca59f180944e9a8675dca78e72002
来源数据集
uspto-grants-2014_02
专利号
US08658646B2

反应笔记

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