1,2-Dichloroethane → HCID 53380046, compound

HRID 515222Notes

Reaction equation

HRID 515222 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.[CH2:26](Cl)[CH2:27]Cl.[CH:30]1[CH:31]=CC2N([OH:39])N=N[C:34]=2[CH:35]=1.CCN([CH:46]([CH3:48])[CH3:47])C(C)C.C[N:50]1[C:54](=[O:55])[CH2:53][CH2:52][CH2:51]1>CO>[C:51]([C:52]1[CH:34]=[CH:35][CH:30]=[CH:31][C:53]=1[C:54]([NH:22][CH2:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([C:13]2[CH:12]=[CH:11][C:10]3[N:6]([CH2:5][CH:2]4[CH2:4][CH2:3]4)[S:7](=[O:24])(=[O:25])[N:8]([CH3:23])[C:9]=3[CH:14]=2)[CH:16]=1)=[O:55])#[N:50].[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][N:22]4[C:27](=[O:39])[C:26]5[C:53](=[CH:52][CH:48]=[CH:46][CH:47]=5)[C:54]4=[O:55])=[CH:14][C:9]=3[N:8]([CH3:23])[S:7]2(=[O:24])=[O:25])[CH2:4][CH2:3]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 13387N-methyl-2-pyrrolidoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67408808HCID 67408808, compound

Product 2

HCID 53380046HCID 53380046, compoundHCID 53380047HCID 53380047, 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) (0.025 g, 0.066 mmol), EDC (0.016 g, 0.086 mmol), HOBt (0.012 g, 0.086 mmol), NMP (1 mL), and finally DIPEA (0.024 mL, 0.14 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-cyano-N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}benzamide (23-3) as a tan solid and 2-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}-1H-isoindole-1,3(2H)-dione (23-4) as a tan solid.

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-003b799ec74840479c36e6c7f7d3c21a
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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