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 246169ノート

反応式

HRID 246169 の反応式
[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

参加物

6

反応物 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

生成物 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収率 47.7%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-311ca59f180944e9a8675dca78e72002
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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