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

HRID 501228

反応式

HRID 501228 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.[N:31]1([C:37]2[CH:45]=[CH:44][C:40]([C:41](Cl)=[O:42])=[CH:39][CH:38]=2)[CH2:36][CH2:35][O:34][CH2:33][CH2:32]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:41](=[O:42])[C:40]3[CH:39]=[CH:38][C:37]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[CH:45][CH:44]=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 866323114-(4-Morpholinyl)benzoyl chloride dihydrochloride

生成物 1

HCID 68462978tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-(4-morpholin-4-ylbenzoylamino)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate収率 32.3%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
25 °C

実験手順

0.40 g (0.998 mmol) of tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate dissolved in 10 ml of pyridine is placed in a 50 ml round-bottomed flask under argon. 0.25 g (0.996 mmol) of 4-(4-morpholinyl)benzoyl chloride dihydrochloride (prepared according to WO 95/04729) is 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: 99/1 dichloromethane/methanol). 0.19 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-(4-morpholin-4-ylbenzoylamino)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate is thus obtained in the form of a yellow foam. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.61 (s, 9H); 1.70 (s, 6H); 3.29 (masked m, 4H); 3.75 (m, 4H); 7.03 (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); 7.97 (d, J=8.5 Hz, 2H); 8.69 (s, 1H); 11.1 (broad m, 1H). LC-MS-DAD-ELSD: 591(+)=(M+H)(+); 535(+)=591(+)-tBu+H.

後処理

  1. customis placed in a 50 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: 99/1 dichloromethane/methanol)

出典と根拠

ORDレコード
ord-cb2af4c964504a4d8d98988942acd4d3
出典データセット
uspto-grants-2010_08
特許番号
US07772261B2

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