Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide

HRID 245888

반응식

HRID 245888 반응식
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]([OH:32])=O)=[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]1[CH2:77][CH2:76][C@H:75]([OH:78])[CH2:74]1>CN(C=O)C>[OH:78][C@@H:75]1[CH2:76][CH2:77][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])([CH3:39])[CH3:38])[CH:28]=2)=[O:32])[CH2:74]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 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280026cis-3-Amino-cyclopentanol trifluoroacetate

생성물 1

HCID 712882622-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide수율 35%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

In a round-bottomed flask, cis-3-amino-cyclopentanol trifluoroacetate (crude from Step 2) was dissolved in DMF (1.2 ml) and N,N-diisopropylethylamine (0.40 ml, 2.3 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 (120 mg, 0.27 mmol) and HATU (114 mg, 0.30 mmol) were added. The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then concentrated. The residue was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-4% MeOH) to afford 50 mg (35%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide as a light yellow solid.

후처리

  1. customthen quenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washThe combined organic layers were washed twice with water and once with brine
  4. concentrationthen concentrated
  5. customThe residue was absorbed on silica gel
  6. customchromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-4% MeOH)

출처 및 근거

ORD 기록
ord-c4fb144a409b4d03bcf13914101c00e1
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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