Triethylamine → HCID 67408811, compound

HRID 515230Notes

Reaction equation

HRID 515230 reaction equation
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[N:20]=[C:19]([CH2:21]O)[CH:18]=[CH:17][C:16]=3[CH3:23])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[CH3:40][S:41]([N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)(=[O:43])=[O:42].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[C:16]([CH3:23])=[CH:17][CH:18]=[C:19]([CH2:21][N:47]4[CH2:48][CH2:49][N:44]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:45][CH2:46]4)[N:20]=3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 67410825HCID 67410825, compound

Product 1

HCID 67408811HCID 67408811, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)methanol (26-6) (25 mg, 0.06 mmol, 1 eq) was dissolved in NMP (0.5 mL) and triethylamine (0.03 mL, 0.18 mmol, 3.0 eq) was added followed by mesyl chloride (0.01 mL, 0.12 mmol, 2.0 eq). After 10 minutes, 1-(methylsulfonyl)piperazine (20.8 mg, 0.13 mmol, 2.0 eq) and DIPEA (0.033 mL, 0.19 mmol, 3.0 eq) were added. The resulting mixture stirred at 80° C. for 10 minutes. The mixture was cooled and purified by reverse phase chromatography (Waters Sunfire MSC18, 15-65% acetonitrile in water with 0.1% TFA modifier) to afford 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(3-methyl-6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (26-7) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.91 (d, J=7.6 Hz, 1 H); 7.48 (d, J=7.6 Hz, 1 H); 7.25 (dd, J=1.6, 8.4 Hz, 1 H); 7.19 (s, 1 H); 7.13 (d, J=8.0 Hz, 1 H); 4.53 (s, 2 H); 3.97 (d, J=7.2 Hz, 2 H); 3.56 (m, 4 H); 3.49 (m, 4 H); 3.33 (s, 3 H); 2.95 (s, 3 H); 2.43 (s, 3 H); 2.21 (m, 1 H); 1.64 (m, 1 H); 1.42 (m, 1H). HRMS m/z (M+H) 542.1693 found, 542.1702 required.

Workup

  1. temperatureThe mixture was cooled
  2. custompurified by reverse phase chromatography (Waters Sunfire MSC18, 15-65% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-e110ab42f8ad4d44828f7acf5c02676b
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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