Acetic Acid → 2-[3-(4-Chlorophenyl)ureido]-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483201Notes

Reaction equation

HRID 1483201 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.C(O)(=O)C.[CH:35]1([CH:38]=O)[CH2:37][CH2:36]1.C([BH3-])#N.[Na+]>CO.O1CCCC1>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][N:23]([CH2:38][CH:35]4[CH2:37][CH2:36]4)[CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5003444Sodium cyanoborohydrideHCID 1182698802-[3-(4-Chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide trifluoroacetate

Product 1

HCID 1182705102-[3-(4-Chlorophenyl)ureido]-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamideYield 94%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranCatalystHCID 887MethanolSolvent

Procedure

To a slurry of compound A4 (300 mg, 0.645 mmol) in methanol (4 mL) and tetrahydrofuran (2 mL) two drops of glacial acetic acid and cyclopropanecarbaldehyde (94.0 mg, 1.34 mmol) were added. After stirring at room temperature for 5 min, sodium cyanoborohydride (122 mg, 1.94 mmol) was added and the reaction mixture was stirred for an additional 3 h. After this time, the reaction was quenched with water (25 mL) and saturated aqueous sodium bicarbonate (50 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was triturated with methylene chloride to afford compound A5 as a white solid (245 mg, 94%): 1H NMR (500 MHz, DMSO-d6) δ 10.95 (s, 1H), 10.16 (s, 1H), 7.54-7.40 (m, 3H), 7.33 (d, J=9.0 Hz, 2H), 6.83 (bs, 1H), 3.54 (s, 2H), 2.84-2.78 (m, 2H), 2.78-2.69 (m, 2H), 2.36 (s, 2H), 0.95-0.87 (m, 1H), 0.53-0.45 (m, 2H), 0.17-0.09 (m, 2H). MS (M+H) 405.

Workup

  1. stirringthe reaction mixture was stirred for an additional 3 h
  2. customAfter this time, the reaction was quenched with water (25 mL) and saturated aqueous sodium bicarbonate (50 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (100 mL)
  4. dry with materialThe extracts were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was triturated with methylene chloride

Sources & evidence

ORD record
ord-2e23abd9a6af47ff99416d6d7b991f2c
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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