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2-(Methylsulfonyl)ethanamine → 2,4-Difluoro-N-{2-fluoro-5-[2-(1-methylethyl)-5-(2-{[2-(methylsulfonyl)ethyl]amino}-4-pyrimidinyl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide

HRID 1670989
ノート
印刷プレビュー

反応式

HRID 1670989 の反応式
[CH3:1][S:2]([CH2:5][CH2:6][NH2:7])(=[O:4])=[O:3].Cl[C:9]1[N:14]=[C:13]([C:15]2[S:19][C:18]([CH:20]([CH3:22])[CH3:21])=[N:17][C:16]=2[C:23]2[CH:24]=[CH:25][C:26]([F:41])=[C:27]([NH:29][S:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=3[F:40])(=[O:32])=[O:31])[CH:28]=2)[CH:12]=[CH:11][N:10]=1>C(O)(C)C>[F:40][C:34]1[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=1[S:30]([NH:29][C:27]1[CH:28]=[C:23]([C:16]2[N:17]=[C:18]([CH:20]([CH3:21])[CH3:22])[S:19][C:15]=2[C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:7][CH2:6][CH2:5][S:2]([CH3:1])(=[O:4])=[O:3])[N:14]=2)[CH:24]=[CH:25][C:26]=1[F:41])(=[O:32])=[O:31]
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

4

反応物 2

HCID 43405612-(Methylsulfonyl)ethanamineHCID 57989690N-{5-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,4-difluorobenzenesulfonamide

生成物 1

HCID 579898802,4-Difluoro-N-{2-fluoro-5-[2-(1-methylethyl)-5-(2-{[2-(methylsulfonyl)ethyl]amino}-4-pyrimidinyl)-1,3-thiazol-4-yl]phenyl}benzenesulfonamide収率 46.9%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
55 °C

実験手順

[2-(Methylsulfonyl)ethyl]amine (352 mg, 2.86 mmol) and N-{5-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,4-difluorobenzenesulfonamide (150 mg, 0.286 mmol) were combined and heated to 55° C. overnight. Isopropanol (1 mL) was added to the reaction mixture and stirred an additional 30 min. The reaction mixture was cooled to rt and partitioned between DCM and 10% aqueous HCl. The organic layer was separated and dried over MgSO4, filtered, and concentrated over silica gel. The crude product was chromatographed on silica gel eluting with 100% DCM to 6:4 [DCM:(9:1 EtOAc:MeOH)]. The clean fractions were combined and concentrated to obtain the title compound as a white foam (82.1 mg; 45% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.65 (s, 1H) 8.14 (d, J=4.2 Hz, 1H) 7.72 (q, J=7.6 Hz, 1H) 7.54 (t, J=9.7 Hz, 1H) 7.47 (br. s., 1H) 7.30-7.42 (m, 2H) 7.11-7.30 (m, 2H) 6.23 (d, J=1.2 Hz, 1H) 3.64 (d, J=0.9 Hz, 2H) 3.20-3.40 (m, 2H range includes water peak) 2.99 (s, 3H) 1.33 (d, J=6.7 Hz, 6H). MS (ESI): 612.2 [M+H]+.

後処理

  1. temperatureThe reaction mixture was cooled to rt
  2. custompartitioned between DCM and 10% aqueous HCl
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated over silica gel
  7. customThe crude product was chromatographed on silica gel eluting with 100% DCM to 6:4 [DCM:(9:1 EtOAc:MeOH)]
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-d6903399cc2f4f3bada2450d7d1c687c
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07994185B2

反応ノート

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