Sodium Chloride → HCID 68464926, compound

HRID 501232

Reaction equation

HRID 501232 reaction equation
[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.[S:29]1[CH:33]=[CH:32][C:31]([C:34](Cl)=[O:35])=[CH:30]1.[Cl-].[Na+]>N1C=CC=CC=1.O1CCCC1>[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:34]([C:31]3[CH:32]=[CH:33][S:29][CH:30]=3)=[O:35])[C:6]=2[N:7]=1)=[O:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:20]

Participants

6

Reactant 3

HCID 5234Sodium ChlorideHCID 27763773-Thenoyl chlorideHCID 68464944tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate

Product 1

HCID 68464926HCID 68464926, compoundYield 28.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

0.20 g (0.50 mmol) of tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate dissolved in 5 ml of pyridine is placed in a 50 ml round-bottomed flask under argon. A solution of 0.07 g (0.50 mmol) of thiophene-3-carbonyl chloride (prepared according to FR 2 411 188) in 2.0 ml of tetrahydrofuran is then added dropwise 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 30 ml of dichloromethane and 30 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). 0.074 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[(thiophene-3-carbonyl)amino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate is thus obtained in the form of a cream-coloured foam. 0.14 g of an impure batch is also obtained, and is repurified by flash chromatography (msilica=30 g; eluent: 95/5 dichloromethane/methanol). 0.013 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[(thiophene-3-carbonyl)amino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate is thus obtained in the form of a cream-coloured foam, along with 0.11 g of an impure batch, which is repurified by flash chromatography (msilica=30 g; eluent: 95/5 dichloromethane/methanol). 0.04 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-[(thiophene-3-carbonyl)amino]-1H-pyrazolo[4,3-d]thiazole-1-carboxylate is thus obtained in the form of a cream-coloured foam. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.62 (s, 9H); 1.71 (s, 6H); 7.20 (t, J=7.5 Hz, 1H); 7.30 (t, J=7.5 Hz, 2H); 7.41 (d, J=7.5 Hz, 2H); 7.70 (d, J=2.0 Hz, 2H); 8.50 (t, J=2.0 Hz, 1H); 8.70 (s, 1H); 11.25 (s, 1H). LC-MS-DAD-ELSD: 510(−)=(M−H)(−); 512(+)=(M+H)(+).

Workup

  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: 95/5 dichloromethane/methanol)

Sources & evidence

ORD record
ord-0adc8299841f494ab9c5d2807be3dc33
Source dataset
uspto-grants-2010_08
Patent number
US07772261B2

Linked notes

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