Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide

HRID 245925ノート

反応式

HRID 245925 の反応式
C(N(CC)C(C)C)(C)C.[F:10][C:11]1[CH:19]=[C:18]2[C:14]([C:15]([C:21]3[N:22]=[C:23]4[C:29]([C:30](O)=[O:31])=[CH:28][N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:24]4=[N:25][CH:26]=3)=[N:16][N:17]2[CH3:20])=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[NH2:72][C@H:73]([CH2:81][CH2:82][CH3:83])[C:74]([N:76]1[CH2:79][CH:78]([F:80])[CH2:77]1)=[O:75]>CN(C=O)C>[F:80][CH:78]1[CH2:77][N:76]([C:74]([C@H:73]([NH:72][C:30]([C:29]2[C:23]3[C:24](=[N:25][CH:26]=[C:21]([C:15]4[C:14]5[C:18](=[CH:19][C:11]([F:10])=[CH:12][CH:13]=5)[N:17]([CH3:20])[N:16]=4)[N:22]=3)[N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:38])[CH3:39])[CH:28]=2)=[O:31])[CH2:81][CH2:82][CH3:83])=[O:75])[CH2:79]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 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280296(R)-2-amino-1-(3-fluoro-azetidin-1-yl)-pentan-1-one trifluoroacetate

生成物 1

HCID 712882122-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide収率 86%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

In a round-bottomed flask, (R)-2-amino-1-(3-fluoro-azetidin-1-yl)-pentan-1-one trifluoroacetate (crude from Step 2) was dissolved in DMF (1.5 ml) and N,N-diisopropylethylamine (0.60 ml, 3.44 mmol) was added. Then 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.25 mmol) and HATU (104 mg, 0.27 mmol) were added. The yellow reaction mixture was stirred at room temperature overnight then quenched with water and diluted with petroleum ether. The resulting suspension was filtered. The filter cake was washed with water and petroleum ether then dried under high vacuum to afford 128 mg (86%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide as an off-white powder.

後処理

  1. customthen quenched with water
  2. additiondiluted with petroleum ether
  3. filtrationThe resulting suspension was filtered
  4. washThe filter cake was washed with water and petroleum ether
  5. customthen dried under high vacuum

出典と根拠

ORDレコード
ord-58ba88fc7b1d40c6ab6116236c0fafb0
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…