Sodium Chloride → tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate

HRID 501227

反応式

HRID 501227 の反応式
[NH2:1][C:2]1[C:6]2[N:7]=[C:8]([C:10](=[O:21])[NH:11][C:12]([CH3:20])([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:13])[S:9][C:5]=2[N:4]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[N:3]=1.Cl.Cl.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C:38]2[CH:46]=[CH:45][C:41]([C:42](Cl)=[O:43])=[CH:40][CH:39]=2)[CH2:34][CH2:33]1.[Cl-].[Na+]>N1C=CC=CC=1>[CH3:13][C:12]([NH:11][C:10]([C:8]1[S:9][C:5]2[N:4]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[N:3]=[C:2]([NH:1][C:42](=[O:43])[C:41]3[CH:40]=[CH:39][C:38]([N:35]4[CH2:34][CH2:33][N:32]([CH3:31])[CH2:37][CH2:36]4)=[CH:46][CH:45]=3)[C:6]=2[N:7]=1)=[O:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:20]

参加物

5

反応物 3

HCID 5234Sodium ChlorideHCID 68464944tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylateHCID 866323104-(4-Methylpiperazin-1-yl)benzoyl chloride dihydrochloride

生成物 1

HCID 68463684tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate収率 43.7%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
25 °C

実験手順

2.0 g (5.0 mmol) of tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate dissolved in 40 ml of pyridine are placed in a 250 ml round-bottomed flask under argon. 1.56 g (5.0 mmol) of 4-(4-methylpiperazin-1-yl)benzoyl chloride dihydrochloride (prepared according to WO 2005/113494) are then gradually added and the mixture is stirred for 15 hours at 25° C. The reaction medium is then concentrated to dryness under reduced pressure (40° C.) and the residue is taken up in 50 ml of dichloromethane and 50 ml of water, and basified with 0.1N sodium hydroxide solution. The emulsion obtained is resorbed by saturation with sodium chloride. After separation of the phases by settling, the organic phase is dried over magnesium sulfate and concentrated to dryness under reduced pressure. The residue is purified by flash chromatography (msilica=30 g; eluent: 95/5 dichloromethane/methanol). 1.32 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate are thus obtained in the form of a yellow foam. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.62 (s, 9H); 1.70 (s, 6H); 2.22 (s, 3H); 2.44 (m, 4H); 3.32 (m, 4H); 7.02 (d, J=8.5 Hz, 2H); 7.20 (t, J=7.5 Hz, 1H); 7.30 (t, J=7.5 Hz, 2H); 7.40 (d, J=7.5 Hz, 2H); 7.95 (d, J=8.5 Hz, 2H); 8.71 (s, 1H); 11.05 (s, 1H). LC-MS-DAD-ELSD: 602(−)=(M−H)(−); 604(+)=(M+H)(+).

後処理

  1. customare placed in a 250 ml round-bottomed flask under argon
  2. concentrationThe reaction medium is then concentrated to dryness under reduced pressure (40° C.)
  3. customThe emulsion obtained
  4. customAfter separation of the phases
  5. dry with materialthe organic phase is dried over magnesium sulfate
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue is purified by flash chromatography (msilica=30 g; eluent: 95/5 dichloromethane/methanol)

出典と根拠

ORDレコード
ord-123243f0c42141c395b332ccc20d99b4
出典データセット
uspto-grants-2010_08
特許番号
US07772261B2

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