Triethylamine → HCID 53380049, compound

HRID 515225Notes

Reaction equation

HRID 515225 reaction equation
[F:1][C:2]1([F:26])[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][CH:16]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[CH3:39][S:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:42])=[O:41].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:16]=[CH:17][CH:18]=[C:19]([CH2:21][N:46]4[CH2:47][CH2:48][N:43]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:44][CH2:45]4)[N:20]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 67413047HCID 67413047, compound

Product 1

HCID 53380049HCID 53380049, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To (6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)methanol (25-1) (30 mg, 0.079 mmol, 1.0 eq) was dissolved in NMP (1 mL) and triethylamine (0.04 mL, 0.24 mmol, 3.0 eq) was added followed by mesyl chloride (0.008 mL, 0.1 mmol, 1.2 eq). After 10 minutes, 1-(methylsulfonyl)piperazine (28.6 mg, 0.17 mmol, 2.1 eq) and DIPEA (0.061 mL, 0.35 mmol, 4.4 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, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (25-2) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.99 (s, 1 H); 7.98 (d, J=8.0 Hz, 1 H); 7.84 (dd, J=1.6, 8.4 Hz, 1 H); 7.77 (d, J=1.6 Hz, 1 H); 7.44 (dd, J=1.6, 6.0 Hz, 1 H); 7.13 (d, J=8.4 Hz, 1 H); 4.66 (s, 2 H); 3.97 (d, J=7.2 Hz, 2 H); 3.62 (brs, 8 H); 3.39 (s, 3 H); 2.99 (s, 3 H); 2.21 (m, 1 H); 1.65 (m, 1 H); 1.44 (m, 1 H). HRMS m/z (M+H) 528.1538 found, 528.1545 required.

Workup

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

Sources & evidence

ORD record
ord-dd92d5a63c654801adfd6f96ccc0cfa1
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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