Potassium Carbonate → HCID 178486247, compound

HRID 736275Notes

Reaction equation

[CH2:1]1[CH2:7][O:6][CH2:5][CH2:4][NH:3][CH2:2]1.Cl.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:16][C:17]1[CH:51]=[CH:50][C:20]([C:21]([NH:23][C:24]2[C:25]3[CH:38]=[C:37]([C:39]([NH:41][N:42]([CH3:49])[C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[O:40])[S:36][C:26]=3[N:27](C(OC(C)(C)C)=O)[N:28]=2)=[O:22])=[CH:19][CH:18]=1.ClCC1C=CC(C(NC2C3C=C(C(NN(C4C=CC(Cl)=CC=4)C)=O)SC=3N(C(OC(C)(C)C)=O)N=2)=O)=CC=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:49][N:42]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[NH:41][C:39]([C:37]1[S:36][C:26]2[NH:27][N:28]=[C:24]([NH:23][C:21](=[O:22])[C:20]3[CH:50]=[CH:51][C:17]([CH2:16][N:3]4[CH2:2][CH2:1][CH2:7][O:6][CH2:5][CH2:4]4)=[CH:18][CH:19]=3)[C:25]=2[CH:38]=1)=[O:40]

Participants

Conditions

Temperature: 25 °C

Procedure

27 mg (74 μmol) of tetrabutylammonium iodide, 153 mg (1.11 mmol) of homomorpholine hydrochloride and 153 mg (1.11 mmol) of potassium carbonate are successively added to a solution of 200 mg (0.37 mmol) of an approximately 70:30 mixture of tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate and tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl)-thieno[2,3-c]pyrazole-1-carboxylate in 6 mL of dimethylformamide under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 16 hours, and then poured onto ice. It is then extracted twice with a 50/50 mixture of ethyl acetate and heptane. The organic extracts are combined, dried over magnesium sulfate and then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is dissolved in 4 mL of methanol and the solution is introduced into a microwave oven tube. The tube is stoppered and the reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes. The reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is purified by preparative LC/MS (conditions B). 34 mg of N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]-4-perhydro-1,4-oxazepin-4-ylmethylbenzamide are thus obtained in the form of a yellow powder melting from 174 to 179° C. LC-MS-DAD-ELSD: 505(+)=(M+H)(+). 38 mg of N-{5-[N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl]-1H-thieno[2,3-c]pyrazol-3-yl}-4-perhydro-1,4-oxazepin-4-ylmethylbenzamide are isolated in the same manner, in the form of a yellow powder. 1H NMR (400 MHz, (CD3)2SO-d6, δ in ppm): This is the salt of the expected structure, with 2.08 (m, 2H); from 3.13 to 4.07 (m, 8H); 3.18 (s, 3H); 4.50 (broad s, 2H); 6.82 (d, J=9.0 Hz, 2H); 7.25 (d, J=9.0 Hz, 2H); 7.70 (broad d, J=8.0 Hz, 2H); 8.17 (partially masked d, J=8.0 Hz, 2H); 8.18 (s, 1H); 9.75 (broad multiplet, 1H); 10.85 (s, 1H); 11.3 (s, 1H); 12.95 (very broad m, 1H).

Workup

additionpoured onto ice
extractionIt is then extracted twice with a 50/50 mixture of ethyl acetate and heptane
dry with materialdried over magnesium sulfate
concentrationconcentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
dissolutionThe residue is dissolved in 4 mL of methanol
additionthe solution is introduced into a microwave oven tube
customthe reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes
concentrationThe reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
customThe residue is purified by preparative LC/MS (conditions B)

Sources & evidence

ORD record: ord-1db51f92ff5044e58871e318e1fe0f79
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595320B2

Reaction notes

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