Diisopropylethylamine → 1-[(2,2-Difluorocyclopropyl)methyl]-5-{4-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]phenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

HRID 515234Notes

Reaction equation

HRID 515234 reaction equation
Cl.[F:2][C:3]1([F:31])[CH2:5][CH:4]1[CH2:6][N:7]1[C:15]2[C:10](=[N:11][C:12]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)[N:9]([CH3:28])[S:8]1(=[O:30])=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:56]1[CH:60]=[CH:59][C:58]([C:61](O)=[O:62])=[N:57]1.CCN(C(C)C)C(C)C>CO.CN1C(=O)CCC1>[F:31][C:3]1([F:2])[CH2:5][CH:4]1[CH2:6][N:7]1[C:15]2[C:10](=[N:11][C:12]([C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:23][CH2:24][N:25]([C:61]([C:58]5[CH:59]=[CH:60][O:56][N:57]=5)=[O:62])[CH2:26][CH2:27]4)=[CH:20][CH:21]=3)=[CH:13][CH:14]=2)[N:9]([CH3:28])[S:8]1(=[O:29])=[O:30]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112864533-Isoxazolecarboxylic acidHCID 866879041-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-(4-piperazin-1-ylphenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide hydrochloride

Product 1

HCID 682450391-[(2,2-Difluorocyclopropyl)methyl]-5-{4-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]phenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a microwave vial was added 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4-piperazin-1-ylphenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide hydrochloride (8-3) (0.028 g, 0.059 mmol), HATU (0.029 g, 0.077 mmol), isoxazole-3-carboxylic acid (0.0087 g, 0.077 mmol), NMP (1 mL), and finally DIPEA (0.060 mL, 0.344 mmol). The reaction mixture was then stirred at room temperature for 1 hour. The crude reaction mixture was then diluted with methanol, then filtered. Purification of crude reaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water) to give 1-[(2,2-difluorocyclopropyl)methyl]-5-{4-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]phenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (34-1) as a tan solid. HRMS (M+H)+: observed=531.1613, calculated=531.1621.

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered
  3. customPurification of crude
  4. customreaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water)

Sources & evidence

ORD record
ord-21e6e9d0d0fe44a99239552f4ba4d9e6
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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