Chloroacetaldehyde → 6-(2-Chloroethyl)-2-[3-(4-chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483203Notes

Reaction equation

HRID 1483203 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:11][CH:10]=1.S([O-])([O-])(=O)=O.[Mg+2].[Cl:37][CH2:38][CH:39]=O.C([BH3-])#N.[Na+]>CO.O1CCCC1.C(O)(=O)C.C(=O)(O)[O-].[Na+]>[Cl:37][CH2:38][CH2:39][N:23]1[CH2:24][CH2:25][C:20]2[C:19]([C:27]([NH2:29])=[O:28])=[C:18]([NH:17][C:16]([NH:15][C:12]3[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=3)=[O:30])[S:26][C:21]=2[CH2:22]1

Participants

9

Reactant 4

HCID 33ChloroacetaldehydeHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 1182698802-[3-(4-Chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide trifluoroacetate

Product 1

HCID 1182698736-(2-Chloroethyl)-2-[3-(4-chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamideYield 99%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a slurry of compound A4 (200 mg, 0.431 mmol) and magnesium sulfate (2 g) in methanol (4 mL) and tetrahydrofuran (2 mL) was added two drops of glacial acetic acid and 2-chloroacetaldehyde (45% in water, 0.340 mL, 1.95 mmol). After stirring at room temperature for 5 min, sodium cyanoborohydride (271 mg, 4.31 mmol) was added and the reaction mixture was stirred for an additional 16 h at room temperature. After this time, the reaction was diluted with saturated aqueous sodium bicarbonate (100 mL), sonicated, and filtered. The filter cake was washed with water (50 mL) and triturated with methylene chloride to afford compound B1 as a white solid (176 mg, 99%): 1H NMR (300 MHz, DMSO-d6) δ 10.94 (s, 1H), 10.19 (s, 1H), 7.57-7.29 (m, 5H), 6.87 (bs, 1H), 3.76 (t, J=6.6 Hz, 2H), 3.57 (s, 2H), 2.87-2.71 (m, 6H). MS (M+H) 413.

Workup

  1. stirringthe reaction mixture was stirred for an additional 16 h at room temperature
  2. customsonicated
  3. filtrationfiltered
  4. washThe filter cake was washed with water (50 mL)
  5. customtriturated with methylene chloride

Sources & evidence

ORD record
ord-5dfb5ac97b6f4a21bdded7217f88a4bf
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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