Water → HCID 23283238, compound

HRID 370122Notes

Reaction equation

HRID 370122 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:31])[C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=2[NH:19][C:20]([C:22]2[S:23][CH:24]=[C:25]([CH2:28][NH:29][CH3:30])[C:26]=2[Cl:27])=[O:21])=[N:6][CH:7]=1.Br[CH2:33][CH2:34][N:35]=[C:36]=O.[NH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.[OH2:43]>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:31])[C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=2[NH:19][C:20]([C:22]2[S:23][CH:24]=[C:25]([CH2:28][NH:29][C:30]([N:35]([CH3:36])[CH2:34][CH2:33][N:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)=[O:43])[C:26]=2[Cl:27])=[O:21])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 31268PyrrolidineHCID 42559572-Bromoethyl isocyanateHCID 16731825HCID 16731825, compound

Product 1

HCID 23283238HCID 23283238, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide (0.70 g, 1.4 mmol) in THF (10 mL) at 0° C. was added 2-bromoethylisocyanate (0.63 mL, 4.2 mmol) and the mixture stirred at ambient temperature. After 30 minutes, the mixture was cooled, concentrated in vacuo and the residue dissolved in DMF (4 mL). Pyrrolidine (0.50 g, 7.0 mmol) was added. The reaction was stirred for 1 hour and poured into water and ethyl acetate. The ethyl acetate layer was dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 0.050 g of N-(5-chloropyridin-2-yl)-2-[((4-((N'-methyl-N'-(2-(pyrrolidin-1-yl)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; NMR (DMSO-d6 /TFA) 10.9 (s, 1), 9.6 (m,1), 9.4 (s, 1), 8.3 (d, 1), 8.1 (d, 1), 7.9 (dd, 1), 7.5 (s, 1), 7.4 (s, 1), 7.3 (s, 1), 4.4 (s, 2), 3.9 (s, 3), 3.6 (m, 2), 3.4 (m, 2), 3.2 (m, 2), 3.0 (m, 2), 2.9 (s, 3), 2 (m, 2), 1.8 (m, 2) ppm.

Workup

  1. temperaturethe mixture was cooled
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue dissolved in DMF (4 mL)
  4. stirringThe reaction was stirred for 1 hour
  5. dry with materialThe ethyl acetate layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-f71f743721994888a181817d7dd0c93d
Source dataset
uspto-grants-2000_10
Patent number
US06140351

Reaction notes

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