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Dicyclohexylcarbodiimide → (S)-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-((methylthio)methyl)-N-(6 (2 (2 (trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridin-2-yl)acetamide

HRID 1054482
ノート
印刷プレビュー

反応式

HRID 1054482 の反応式
[CH3:1][S:2][CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[CH:12]=[N:13][C:14]([N:17]3[CH2:21][CH2:20][CH2:19][C@H:18]3[C:22]([F:25])([F:24])[F:23])=[N:15][CH:16]=2)[N:6]=1.C1CCC(N=C=NC2CCCCC2)CC1.[N:41]1([C:52](=[O:53])[C:51]2[N:50]([CH2:54][C:55](O)=[O:56])[CH:49]=[N:48][C:47]=2[N:45]([CH3:46])[C:43]1=[O:44])[CH3:42]>N1C=CC=CC=1.C(Cl)Cl>[CH3:42][N:41]1[C:52](=[O:53])[C:51]2[N:50]([CH2:54][C:55]([N:4]([CH2:3][S:2][CH3:1])[C:5]3[CH:10]=[CH:9][CH:8]=[C:7]([C:11]4[CH:16]=[N:15][C:14]([N:17]5[CH2:21][CH2:20][CH2:19][C@H:18]5[C:22]([F:25])([F:23])[F:24])=[N:13][CH:12]=4)[N:6]=3)=[O:56])[CH:49]=[N:48][C:47]=2[N:45]([CH3:46])[C:43]1=[O:44]
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

6

反応物 3

HCID 10868Dicyclohexylcarbodiimide2 回HCID 69550Acefylline2 回HCID 86727119(S)-N-((methylthio)methyl)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridine-2-amine

生成物 1

HCID 86727120(S)-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-((methylthio)methyl)-N-(6 (2 (2 (trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridin-2-yl)acetamide収率 68.3%

試薬・触媒・溶媒

2
HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

A solution of (S)—N-((methylthio)methyl)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridine-2-amine (Intermediate 4.17 g, 46.0 mmol) and DCC (18.99 g, 92 mmol) in pyridine (230 mL) was heated for 30 minutes at 60° C. before theophylline 7-acetic acid (21.92 g, 92 mmol) was added in one portion. The reaction mixture was stirred at 60° C. and monitored by LCMS. After 2 hours, additional theophylline 7-acetic acid (21.92 g, 92 mmol) and DCC (18.99 g, 92 mmol) were added to drive the reaction to completion. The reaction mixture was diluted with CH2Cl2. The resulting precipitate (DCC urea) was filtered over Celite® and washed with CH2Cl2 (3×). The mixture was diluted with water and adjusted to pH 3 with aqueous 3M HCl. The organic and aqueous layers were separated and the aqueous layer was extracted with additional CH2Cl2 (3×). The combined organic layers were washed with aqueous 1M HCl (2×), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified using silica gel chromatography, eluting with EtOAc:Hex (70:30) to yield 18.5 g (31.4 mmol, 68%) of the title product as a thick oil; 1H NMR (300 MHz, DMSO-d6) δ 9.21 (s, 2H), 8.16-8.03 (m, 2H), 7.99 (d, J=7.6 Hz, 1H), 7.60 (d, J=7.7 Hz, 1H), 5.33 (s, 2H), 5.12 (m, 3H), 3.82-3.65 (m, 2H), 3.43 (s, 3H), 3.18 (s, 3H), 2.31-2.09 (m, 4H), 2.06 (s, 3H); m/z found [M+H]+=590.37.

後処理

  1. additionwas added in one portion
  2. customthe reaction to completion
  3. filtrationThe resulting precipitate (DCC urea) was filtered over Celite®
  4. washwashed with CH2Cl2 (3×)
  5. additionThe mixture was diluted with water
  6. customThe organic and aqueous layers were separated
  7. extractionthe aqueous layer was extracted with additional CH2Cl2 (3×)
  8. washThe combined organic layers were washed with aqueous 1M HCl (2×)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified
  13. washeluting with EtOAc

出典と根拠

ORDレコード
ord-d563b37b9d214ca7894d3a74054825d4
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09394308B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート