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Diisopropylethylamine → N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842806
ノート
印刷プレビュー

反応式

HRID 1842806 の反応式
[CH3:1][N:2]([CH3:8])[C@@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.F[C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[CH:27]=[N:28][N:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=34)[CH:23]=[CH:22][N:21]=2)=[C:12]([O:35][CH3:36])[CH:11]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:1][N:2]([CH3:8])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([NH:19][C:20]3[N:25]=[C:24]([C:26]4[CH:27]=[N:28][N:29]5[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=45)[CH:23]=[CH:22][N:21]=3)=[C:12]([O:35][CH3:36])[CH:11]=2)[CH2:4]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 71240784N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2 回

生成物 1

HCID 71269755N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine収率 86%

試薬・触媒・溶媒 1

HCID 31374
Dimethylacetamide
溶媒

反応条件

温度
85 °C

実験手順

(3R)—N,N-Dimethylpyrrolidin-3-amine (0.166 mL, 1.31 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 155, 415 mg, 1.09 mmol) and DIPEA (0.227 mL, 1.31 mmol) in DMA (3.2 mL) and the mixture was heated at 85° C. for 1 h. Part purification was achieved by ion exchange chromatography, using an SCX column, eluting with 7M methanolic ammonia. Clean fractions were combined and concentrated. Further purification by FCC, eluting with 0-7% CH3OH in CH2Cl2 gave the title compound (443 mg, 86%) as an orange solid; 1H NMR: 1.77-1.88 (1H, m), 2.13-2.20 (1H, m), 2.23 (6H, s), 2.75-2.84 (1H, m), 3.14-3.26 (3H, m), 3.43-3.51 (1H, m), 3.96 (3H, s), 6.58 (1H, s), 7.08 (1H, td), 7.27 (1H, d), 7.34-7.39 (1H, m), 8.24 (1H, s), 8.35 (1H, d), 8.40 (1H, s), 8.49 (1H, d), 8.78 (1H, s), 8.80 (1H, d); m/z: ES+ MH+ 475.31.

後処理

  1. customPart purification
  2. washeluting with 7M methanolic ammonia
  3. concentrationconcentrated
  4. customFurther purification by FCC
  5. washeluting with 0-7% CH3OH in CH2Cl2

出典と根拠

ORDレコード
ord-4dd62794a0c94532bbd3bd7b006a2fe4
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08946235B2

反応ノート

読み込み中…

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