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Sodium Carbonate → (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-phenylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one

HRID 407978
ノート
印刷プレビュー

反応式

HRID 407978 の反応式
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([O:19][C:20]4[CH:25]=[C:24]([F:26])[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:22][C:21]=4[F:31])[C:15]3=[O:32])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:31][C:21]1[CH:22]=[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([F:26])=[CH:25][C:20]=1[O:19][C@H:16]1[CH2:17][CH2:18][N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:5]3[N:4]=[CH:3][C:2]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:7][N:6]=3)[CH2:9][CH2:10]2)[C:15]1=[O:32]
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 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 67469711(S)-1-(1-(5-bromopyrimidin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one

生成物 1

HCID 54671279(S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-phenylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one収率 64%

試薬・触媒・溶媒 2

HCID 178418397
HCID 178418397、化合物
触媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

(S)-1-(1-(5-bromopyrimidin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one (Example 90; 80 mg, 0.15 mmol) was dissolved in dioxane (2 mL) and phenylboronic acid (28 mg, 0.23 mmol), 2M Na2CO3 (301 μL, 0.60 mmol) and Pd(PPh3)4 (17 mg, 0.015 mmol) were added and the reaction heated to 95° C. under nitrogen for 2 hours. The reaction was cooled to ambient temperature and partitioned between water and CH2Cl2, and the organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (70% EtOAc in hexanes) to afford impure material. The material was then purified on C18 reverse phase chromatography (20 to 95% ACN in water) to afford (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-phenylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (51 mg, 0.096 mmol, 64% yield) as a white solid. Mass spectrum (apci) m/z=529.3 (M+H).

後処理

  1. temperatureThe reaction was cooled to ambient temperature
  2. custompartitioned between water and CH2Cl2
  3. dry with materialthe organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified over silica gel (70% EtOAc in hexanes)
  7. customto afford impure material
  8. customThe material was then purified on C18 reverse phase chromatography (20 to 95% ACN in water)

出典と根拠

ORDレコード
ord-d366e03f18c34d7a864386e652c2a060
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08754226B2

反応ノート

読み込み中…

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