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Triethylamine → N1-[(3-bromo-4-methylphenyl)methyl]-N1-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,1-cyclopropanedicarboxamide

HRID 657389
ノート
印刷プレビュー

反応式

HRID 657389 の反応式
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:29][CH3:30])=[C:10]([CH2:19][NH:20][C:21]([C:23]3([C:26]([OH:28])=O)[CH2:25][CH2:24]3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].C[N:32](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[Br:62][C:63]1[CH:64]=[C:65]([CH2:70]N)[CH:66]=[CH:67][C:68]=1[CH3:69]>C(Cl)Cl>[Br:62][C:63]1[CH:64]=[C:65]([CH2:70][N:20]([CH2:19][C:10]2[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]3[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]3=[N:8][C:9]=2[CH2:29][CH3:30])[C:21]([C:23]2([C:26]([NH2:32])=[O:28])[CH2:25][CH2:24]2)=[O:22])[CH:66]=[CH:67][C:68]=1[CH3:69]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53414434(3-Bromo-4-methylphenyl)methanamineHCID 578198681-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]cyclopropanecarboxylic acid

生成物 1

HCID 69011639
N1-[(3-bromo-4-methylphenyl)methyl]-N1-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,1-cyclopropanedicarboxamide
収率 8.11%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 1-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]cyclopropanecarboxylic acid (600 mg, 1.444 mmol), HBTU (657 mg, 1.733 mmol), Et3N (1006 μL, 7.22 mmol) and 1-(3-bromo-4-methylphenyl)methanamine (318 mg, 1.589 mmol) in DCM was stirred at room temperature overnight. The reaction mixture was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with brine and then concentrated under vacuum to give the crude residue. It was then purified with a Gilson HPLC (acidic conditions: 0.1% TFA in the solvents), eluting with 10 to 70% CH3CN in water at a flow rate of 20 mL/min. The product fractions were combined and washed with saturated NaHCO3 and extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered and then concentrated under vacuum to give N1-[(3-bromo-4-methylphenyl)methyl]-N1-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,1-cyclopropanedicarboxamide (70 mg, 8.11%). LC-MS m/z 597 M+, 0.88 min (ret time).

後処理

  1. customThe reaction mixture was quenched with saturated NaHCO3
  2. extractionextracted with DCM twice
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated under vacuum
  5. customto give the crude residue
  6. customIt was then purified with a Gilson HPLC (acidic conditions
  7. wash0.1% TFA in the solvents), eluting with 10 to 70% CH3CN in water at a flow rate of 20 mL/min
  8. washwashed with saturated NaHCO3
  9. extractionextracted with ethyl acetate twice
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum

出典と根拠

ORDレコード
ord-4c0d809111324c38808c6337a7469e77
出典データセット
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08071588B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート