Diisopropylethylamine → 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 246169노트

반응식

HRID 246169 반응식
[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

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 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

생성물 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]-amide수율 47.7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-311ca59f180944e9a8675dca78e72002
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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