5-Iodo-7-(triisopropylsilyl)-7H-pyrrolo-[2,3-d]pyrimidine → {6-fluoro-5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester

HRID 1403279ノート

反応式

HRID 1403279 の反応式
I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]=[O:49])=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]([OH:49])[C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)([CH3:29])([CH3:27])[CH3:28]

参加物

5

反応物 3

HCID 509865195-Iodo-7-(triisopropylsilyl)-7H-pyrrolo-[2,3-d]pyrimidineHCID 57963046HCID 57963046、化合物HCID 178418918HCID 178418918、化合物

生成物 1

HCID 57963240{6-fluoro-5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester収率 85.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To 5-iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (38, 30 g, 74.7 mmol) in 300 mL of tetrahydrofuran under an atmosphere of nitrogen at −20° C., isopropylmagnesium chloride (43.6 mL, 2 M in tetrahydrofuran, 87 mmol) was added and the reaction allowed to warm to 0° C. over 30 minutes. The reaction was cooled to −40° C. and (6-fluoro-5-formyl-pyridin-2-yl)-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (66, 17.96 g, 49.8 mmol) in tetrahydrofuran was added. The reaction was allowed to warm to 0° C. over an hour, then quenched with brine and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 0-40% ethyl acetate in hexane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (67, 27 g, 42.5 mmol, 85% yield).

後処理

  1. temperatureThe reaction was cooled to −40° C.
  2. temperatureto warm to 0° C. over an hour
  3. customquenched with brine
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with 0-40% ethyl acetate in hexane
  10. customthe solvents removed under vacuum

出典と根拠

ORDレコード
ord-28b54b0691f646b7ae650aa92c729537
出典データセット
uspto-grants-2014_12
特許番号
US08912204B2

反応ノート

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