Triethylamine → HCID 178479863, compound

HRID 515220Notes

Reaction equation

[F:1][C:2]1([F:28])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:22]=[C:21]([CH2:23]O)[CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:14][C:9]=2[N:8]([CH3:25])[S:7]1(=[O:27])=[O:26].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[O:41]1[C:49]2[CH2:48][CH2:47][NH:46][CH2:45][C:44]=2[C:43]([OH:50])=[N:42]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:28][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:22]=[C:21]([CH2:23][N:46]4[CH2:47][CH2:48][C:49]5[O:41][N:42]=[C:43]([OH:50])[C:44]=5[CH2:45]4)[CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:14][C:9]=2[N:8]([CH3:25])[S:7]1(=[O:27])=[O:26]

Participants

Conditions

Temperature: 80 °C

Procedure

2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-(hydroxymethyl)benzonitrile (4-3) (30 mg, 0.07 mmol, 1 eq) was dissolved in NMP (1 mL) and triethylamine (0.03 mL, 0.22 mmol, 3 eq) was added followed by mesyl chloride (0.006 mL, 0.08 mmil, 1.1 eq). After 10 minutes, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (23.2 mg, 0.16 mmol, 2 eq) and DIPEA (0.085 mL, 0.49 mmol, 6 eq) were added. The resulting mixture stirred at 80° C. for 1 h. The mixture was cooled and purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(3-hydroxy-6,7-dihydroisoxazolo[4,5-c]pyridin-5(4H)-yl)methyl]benzonitrile (20-1) as a white solid. HRMS m/z (M+H) 528.1521 found, 528.1512 required.

Workup

temperatureThe mixture was cooled
custompurified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record: ord-b555854115c44055b8f240f8a3f5935c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108937B2

Reaction notes

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