Potassium Carbonate → 2-(4-chlorophenyl)-5-cyclopropyl-6-[2-(3-hydroxyazetidin-1-yl)ethyl-methylsulfonyl-amino]-N-methyl-indazole-3-carboxamide

HRID 63546

反応式

HRID 63546 の反応式
Br[CH2:2][CH2:3][N:4]([S:28]([CH3:31])(=[O:30])=[O:29])[C:5]1[C:6]([CH:25]2[CH2:27][CH2:26]2)=[CH:7][C:8]2[C:12]([CH:13]=1)=[N:11][N:10]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:9]=2[C:21]([NH:23][CH3:24])=[O:22].Cl.[NH:33]1[CH2:36][CH:35]([OH:37])[CH2:34]1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([N:10]2[C:9]([C:21]([NH:23][CH3:24])=[O:22])=[C:8]3[C:12]([CH:13]=[C:5]([N:4]([CH2:3][CH2:2][N:33]4[CH2:36][CH:35]([OH:37])[CH2:34]4)[S:28]([CH3:31])(=[O:30])=[O:29])[C:6]([CH:25]4[CH2:27][CH2:26]4)=[CH:7]3)=[N:11]2)=[CH:15][CH:16]=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 27592903-Hydroxyazetidine hydrochlorideHCID 866990036-[2-bromoethyl(methylsulfonyl)amino]-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-indazole-3-carboxamide

生成物 1

HCID 717685842-(4-chlorophenyl)-5-cyclopropyl-6-[2-(3-hydroxyazetidin-1-yl)ethyl-methylsulfonyl-amino]-N-methyl-indazole-3-carboxamide

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred solution of 6-[2-bromoethyl(methylsulfonyl)amino]-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-indazole-3-carboxamide (5 mg, 0.01 mmol) in MeCN (500 uL) was added azetidin-3-ol hydrochloride (6.6 mg, 0.06 mmol) followed by potassium carbonate (6 mg). The resultant suspension was heated at 65 deg C. in a sealed vial and after 3 days, cooled to RT then filtered through a cotton wool plug. The residue was washed with MeCN (2 mL) and the volatiles removed in vacuo. The residual colourless oil was purified by preparative HPLC/MS (MeCN/0.1% formic acid in water (v/v)—gradient elution) to give Compound (22) as a white amorphous solid (4.5 mg, 91%). 1H NMR (400 MHz, CD3CN) δ 7.90 (s, 1H), 7.63-7.53 (m, 4H), 7.42 (s, 1H), 7.03 (br s, 1H), 4.67-4.40 (m, 2H), 4.17 (br s, 2H), 3.96 (br s, 2H), 3.80 (br s, 1H), 3.38 (br s, J=41.2 Hz, 2H), 3.16 (s, 3H), 2.91 (d, J=4.8 Hz, 3H), 2.34-2.33 (m, 1H), 1.18-1.01 (m, 3H), 0.68-0.58 (m, 1H). ESI-MS m/z calculated for [M+H]+: 518.16. found: 518.10.

後処理

  1. filtrationthen filtered through a cotton wool plug
  2. washThe residue was washed with MeCN (2 mL)
  3. customthe volatiles removed in vacuo
  4. customThe residual colourless oil was purified by preparative HPLC/MS (MeCN/0.1% formic acid in water (v/v)—gradient elution)

出典と根拠

ORDレコード
ord-327e886468914a97976c3325f6dbe39c
出典データセット
uspto-grants-2016_09
特許番号
US09447080B2

関連ノート

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