Isopropanol → 2-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-isopropoxy-7-methyl-7,9-dihydro-8H-purin-8-one

HRID 510115

반응식

HRID 510115 반응식
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)=[C:16](I)[N:15]=2)=[N:6]1.[CH:30]([OH:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C>[Cu]I.CN1CCCC1=O>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)=[C:16]([O:33][CH:30]([CH3:32])[CH3:31])[N:15]=2)=[N:6]1

참가 물질

7

반응물 4

HCID 3776IsopropanolHCID 10796Cesium carbonateHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 867200522-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-iodo-7-methyl-7,9-dihydro-8H-purin-8-one

생성물 1

HCID 666143192-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-isopropoxy-7-methyl-7,9-dihydro-8H-purin-8-one

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
140 °C

실험 절차

200 mg (0.399 mmol) of the compound obtained in example 107 were admixed in a microwavable flask with isopropanol (3 ml), 260 mg (0.798 mmol) of cesium carbonate, 8 mg (0.04 mmol) of copper(I) iodide and 19 mg (0.08 mmol) of 3,4,7,8-tetramethyl-1,10-phenanthroline. The flask was purged with argon while being treated with ultrasound for 5 min, and then closed with an appropriate septum. Then it was heated in a microwave at 140° C. for 2 h. Reaction monitoring showed low conversion. For that reason, N-methylpyrrolidone (1 ml) was added and the mixture was once again heated in a microwave at 140° C. for 2 h and then at 180° C. for 8 h. After cooling, the reaction mixture was filtered and concentrated, and the residue was purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient). 21 mg of the title compound were obtained (12% of theory).

후처리

  1. customThe flask was purged with argon
  2. additionwhile being treated with ultrasound for 5 min
  3. customclosed with an appropriate septum
  4. customReaction monitoring
  5. temperaturethe mixture was once again heated in a microwave at 140° C. for 2 h
  6. temperatureAfter cooling
  7. filtrationthe reaction mixture was filtered
  8. concentrationconcentrated
  9. customthe residue was purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient)

출처 및 근거

ORD 기록
ord-93e140ad3a6242eda03f4f74f49d346d
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096592B2

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