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Diisopropylethylamine → (R,E)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(cyclobutyl(methyl)amino)but-2-en-1-one

HRID 920201
ノート
印刷プレビュー

反応式

HRID 920201 の反応式
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@@H:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[N:3]=1.Cl.[CH:18]1([N:22]([CH3:29])[CH2:23]/[CH:24]=[CH:25]/[C:26](O)=[O:27])[CH2:21][CH2:20][CH2:19]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:26](=[O:27])/[CH:25]=[CH:24]/[CH2:23][N:22]([CH:18]4[CH2:21][CH2:20][CH2:19]4)[CH3:29])[CH2:13]3)[N:3]=[C:2]([I:1])[C:10]=12
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 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71209048(E)-4-(cyclobutyl(methyl)amino)but-2-enoic acid hydrochlorideHCID 71256207(R)-3-iodo-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 71256082
(R,E)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(cyclobutyl(methyl)amino)but-2-en-1-one
収率 118.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a cooled solution of (R)-3-iodo-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4) (990 mg, 3.0 mmol), (E)-4-(cyclobutyl(methyl)amino)but-2-enoic acid (21) (871 mg, 3.0 mmol) and DIPEA (3.1 mL, 18 mmol) in DMF (15 mL) was added HBTU (1.74 g, 4.5 mmol). The resulting solution was stirred at RT overnight, then quenched with water. The layers were separated and the aqueous layer was extracted with 85% DCM/IPA(3×). The combined organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography to provided (R,E)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(cyclobutyl(methyl)amino)but-2-en-1-one (22) (1.71 g, quant. yield) as a white solid. LC-MS (ESI): m/z (M+1) 482.0.

後処理

  1. customquenched with water
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with 85% DCM/IPA(3×)
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-ae310f25cc3b42c3b4c5cc6236da075b
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09273051B2

反応ノート

読み込み中…

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