Ethanol → HCID 69104602, compound

HRID 1244546Notes

Reaction equation

HRID 1244546 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([N:12]([CH3:14])[CH3:13])=[N:7][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCO.[Cl:20][C:21]1[S:25][C:24]([C:26]([NH:28][CH2:29][CH:30]2[CH2:32][O:31]2)=[O:27])=[CH:23][CH:22]=1>O>[NH4+:1].[OH-:9].[CH3:14][N:12]([CH3:13])[C:6]([C:5]1[CH:15]=[CH:16][C:2]([NH:1][CH2:32][CH:30]([OH:31])[CH2:29][NH:28][C:26]([C:24]2[S:25][C:21]([Cl:20])=[CH:22][CH:23]=2)=[O:27])=[CH:3][CH:4]=1)=[N:7][S:8]([CH3:11])(=[O:10])=[O:9]

Participants

6

Reactant 3

HCID 702EthanolHCID 219197985-chloro-N-(2-oxiranylmethyl)-2-thiophenecarboxamideHCID 69104455HCID 69104455, compound

Product 2

HCID 14923Ammonium HydroxideYield 1%HCID 69104602HCID 69104602, compoundYield 97.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Part A: To mixture of 345 mg (1.43 mmol) of 4-amino-N,N-dimethyl-N′-(methylsulfonyl)benzamidine, 1.5 mL of EtOH, and 0.5 mL of H2O heated at 100° C. was added portion-wise 311 mg (1.43 mmol) of 5-chloro-N-(oxiran-2-ylmethyl)thiophene-2-carboxamide. After 8 hours, the volatiles were evaporated and the compound purified by purified by ISCO System flash chromatography (Gradient elution 0% to 100% B over 40 min; (A=Hexane, B=AcOEt) then 0% to 100% B over 30 min; (A=AcOEt, B=5% MeOH and 1% NH4OH)) to yield 320 mg of N-(3-(4-(N,N-dimethyl -N′-(methylsulfonyl)carbamimidoyl)phenylamino)-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide as a yellow oil. Further purification by prep HPLC yield an analytically pure sample. TR=4.758 min (Shimadzu Phenomenex S5 ODS 4.6×50 mm Luna flow rate 2.5 ml/mn; detection at 220 nM; gradient elution 0% to 100% B over 8 min; (A=10% MeOH, 90% H2O, 0.2% H3PO4 & B=90% MeOH, 10% H2O, 0.2% H3PO4). 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J=4.05 Hz, 1H), 7.26 (d, J=8.05 Hz, 2H), 7.02 (d, J=4.05 Hz, 1H), 6.9 (d, J=8.05 Hz, 2H), 3.98 (m, 1H), 3.62 (t, 2H), 3.5 (m, 1H). 3.4 (m, 1H), 3.3 (m, 1H), 3.2 (m, 3H), 2.79 (s, 3H), 2.0 (m, 2H), 1.88 (m, 2H), ppm. LC-MS (ESI) 459.21 [M+H]+. HRMS (ESI) m/z calcd for C18H24N4O4S2Cl [M+H]+ 459.09276, found 459.0917.

Workup

  1. customthe volatiles were evaporated
  2. customthe compound purified
  3. customby purified by ISCO System flash chromatography (
  4. washGradient elution 0% to 100% B over 40 min
  5. wait(A=Hexane, B=AcOEt) then 0% to 100% B over 30 min

Sources & evidence

ORD record
ord-99d0cf3c8da0477fb57b9a73fcf58371
Source dataset
uspto-grants-2006_10
Patent number
US07122557B2

Reaction notes

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