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Sodium hydride → 4-[(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholine

HRID 1710790
ノート
印刷プレビュー

反応式

HRID 1710790 の反応式
[H-].[Na+].[CH3:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][CH2:10][CH2:11][OH:12].Cl[C:14]1[N:19]=[CH:18][C:17]([C:20]2[S:21][C:22]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[C:23]([CH3:25])[N:24]=2)=[CH:16][CH:15]=1>CN(C)C=O>[CH3:25][C:23]1[N:24]=[C:20]([C:17]2[CH:18]=[N:19][C:14]([O:12][CH2:11][CH2:10][CH2:9][N:5]3[CH2:6][CH2:7][CH2:8][CH:4]3[CH3:3])=[CH:15][CH:16]=2)[S:21][C:22]=1[C:26]([N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)=[O:27]
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

5

反応物 3

HCID 24758Sodium hydrideHCID 224016093-(2-Methylpyrrolidin-1-yl)propan-1-olHCID 594574974-{[2-(6-Chloropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]carbonyl}morpholine

生成物 1

HCID 594575194-[(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholine収率 8%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒

反応条件

温度
0 °C

実験手順

Sodium hydride 60% in oil (0.11 g, 2.2 eq, 2.82 mmol) is added to a mixture of 3-(2-methyl-1-pyrrolidinyl)-1-propanol (0.31 g, 2.2 eq, 2.18 mmol) in dimethylformamide (15 ml) cooled to 0° C. The mixture is stirred at 22° C. for 20 min, and cooled again to 0° C. 4-{[2-(6-chloropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]carbonyl}morpholine i99 (0.415 g, 1 eq, 1.28 mmol) is then added to the solution and the mixture is stirred 48 h at room temperature. The solvent is evaporated, and the residue is taken up in ethyl acetate and washed two times with an aqueous solution of sodium hydrogenocarbonate. The organic layer is dried over magnesium sulfate, filtered and concentrated under vacuum. Purification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 97/2.7/0.3) affords 0.047 g of 4-[(4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholine 147.

後処理

  1. temperaturecooled again to 0° C
  2. stirringthe mixture is stirred 48 h at room temperature
  3. customThe solvent is evaporated
  4. washwashed two times with an aqueous solution of sodium hydrogenocarbonate
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 97/2.7/0.3)

出典と根拠

ORDレコード
ord-6c0f031bc20f421bbbcb20c5823d8696
出典データセット
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07790720B2

反応ノート

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