Methanol → US8933228, Ref 2

HRID 593421ノート

反応式

HRID 593421 の反応式
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[C:13]([C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[NH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([O:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:53])[CH2:50][O:51][CH3:52])[CH:43]=2)=[CH:33][CH:32]=1.CO>C(Cl)Cl>[C:13]([C:17]1[CH:21]=[C:20]([NH:22][C:6](=[O:7])[NH:30][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]([O:41][C:42]3[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:53])[CH2:50][O:51][CH3:52])[CH:43]=3)=[CH:33][CH:32]=2)[N:19]([C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14]

参加物

6

反応物 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 66718180N-(4-(4-Aminonaphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide

生成物 1

HCID 46218331US8933228, Ref 2収率 45%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred suspension of CDI (28.8 g, 178 mmol) in DCM (250 mL) at RT, under nitrogen, was added 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (7) (40.7 g, 178 mmol) portion-wise over 1 hr. After 1 hr the resulting dark red solution was added dropwise, over 1 hr, to a stirred solution of N-(4-(4-aminonaphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide (12) (35.5 g, 99 mmol) in DCM (1 L). After 1 hr MeOH (100 mL) was added and the mixture was kept at RT for 16 hr. The reaction mixture was evaporated in vacuo and the residue was taken up into DCM (500 mL) and was washed with water and saturated aqueous NaHCO3 solution (500 mL). The organic layer was dried (MgSO4), evaporated in vacuo and the residue purified by flash column chromatography (SiO2, 800 g, 2% MeOH in DCM, isocratic elution). This product was recrystallized from ethyl acetate/heptane (800 mL of a 5:3 v/v mixture) to afford N-(4-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)pyridin-2-yl)-2-methoxyacetamide (1) (25.5 g, 45%) as a white powder. Found: C, 68.41; H, 5.93; N, 14.36; C33H34N6O4 requires: C, 68.49; H, 5.92; N, 14.52%.

後処理

  1. customThe reaction mixture was evaporated in vacuo
  2. washwas washed with water and saturated aqueous NaHCO3 solution (500 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated in vacuo
  5. customthe residue purified by flash column chromatography (SiO2, 800 g, 2% MeOH in DCM, isocratic elution)
  6. customThis product was recrystallized from ethyl acetate/heptane (800 mL of a 5:3 v/v mixture)

出典と根拠

ORDレコード
ord-3c8ae17e282349b1a801e84a5d4cf549
出典データセット
uspto-grants-2016_01
特許番号
US09242960B2

反応ノート

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