N-methyl-2-pyrrolidone → HCID 53380051, compound

HRID 515223Notes

Reaction equation

HRID 515223 reaction equation
Cl.[CH:2]1([CH2:5][N:6]2[C:10]3[CH:11]=[CH:12][C:13]([C:15]4[CH:16]=[C:17]([CH2:21][NH2:22])[CH:18]=[CH:19][CH:20]=4)=[CH:14][C:9]=3[N:8]([CH3:23])[S:7]2(=[O:25])=[O:24])[CH2:4][CH2:3]1.F[C:27]1[N:34]=[CH:33][CH:32]=[CH:31][C:28]=1[C:29]#[N:30].CN1C(=O)CCC1.CCN(C(C)C)C(C)C>CO>[CH:2]1([CH2:5][N:6]2[C:10]3[CH:11]=[CH:12][C:13]([C:15]4[CH:16]=[C:17]([CH:18]=[CH:19][CH:20]=4)[CH2:21][NH:22][C:27]4[N:34]=[CH:33][CH:32]=[CH:31][C:28]=4[C:29]#[N:30])=[CH:14][C:9]=3[N:8]([CH3:23])[S:7]2(=[O:24])=[O:25])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 27832543-Cyano-2-fluoropyridineHCID 67408808HCID 67408808, compound

Product 1

HCID 53380051HCID 53380051, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 1-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenyl}methanamine hydrochloride (23-2) (0.037 g, 0.097 mmol), 2-fluoronicotinonitrile (0.18 g, 0.15 mmol), NMP (0.7 mL), and finally DIPEA (0.039 mL, 0.22 mmol). The reaction mixture was then heated under microwave irradiation at 100° C. for 10 minutes. The crude reaction mixture was then allowed to cool to room temperature, diluted with methanol, then filtered and concentrated. 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 2-({3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}amino)nicotinonitrile (24-1) as a tan solid. HRMS (M+H)+: observed=446.1642, calculated=446.1645.

Workup

  1. customThe crude reaction mixture
  2. temperatureto cool to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of crude
  6. 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-c1dbad03806a4b04b8a8c9213557d60f
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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