Triethylamine → HCID 53380049、化合物

HRID 515225ノート

反応式

HRID 515225 の反応式
[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[N:20]=[C:19]([CH2:21]O)[CH:18]=[CH:17][CH:16]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[CH3:39][S:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:42])=[O:41].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:16]=[CH:17][CH:18]=[C:19]([CH2:21][N:46]4[CH2:47][CH2:48][N:43]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:44][CH2:45]4)[N:20]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]

参加物

7

反応物 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 67413047HCID 67413047、化合物

生成物 1

HCID 53380049HCID 53380049、化合物

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
80 °C

実験手順

To (6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)methanol (25-1) (30 mg, 0.079 mmol, 1.0 eq) was dissolved in NMP (1 mL) and triethylamine (0.04 mL, 0.24 mmol, 3.0 eq) was added followed by mesyl chloride (0.008 mL, 0.1 mmol, 1.2 eq). After 10 minutes, 1-(methylsulfonyl)piperazine (28.6 mg, 0.17 mmol, 2.1 eq) and DIPEA (0.061 mL, 0.35 mmol, 4.4 eq) were added. The resulting mixture stirred at 80° C. for 10 minutes. The mixture was cooled and purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (25-2) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.99 (s, 1 H); 7.98 (d, J=8.0 Hz, 1 H); 7.84 (dd, J=1.6, 8.4 Hz, 1 H); 7.77 (d, J=1.6 Hz, 1 H); 7.44 (dd, J=1.6, 6.0 Hz, 1 H); 7.13 (d, J=8.4 Hz, 1 H); 4.66 (s, 2 H); 3.97 (d, J=7.2 Hz, 2 H); 3.62 (brs, 8 H); 3.39 (s, 3 H); 2.99 (s, 3 H); 2.21 (m, 1 H); 1.65 (m, 1 H); 1.44 (m, 1 H). HRMS m/z (M+H) 528.1538 found, 528.1545 required.

後処理

  1. temperatureThe mixture was cooled
  2. custompurified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier)

出典と根拠

ORDレコード
ord-dd92d5a63c654801adfd6f96ccc0cfa1
出典データセット
uspto-grants-2015_08
特許番号
US09108937B2

反応ノート

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