Triethylamine → HCID 118270017, compound

HRID 1483225Notes

Reaction equation

HRID 1483225 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(N(CC)CC)C.[C:38]([NH:45][CH2:46][CH2:47][CH2:48]Br)([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>CN(C=O)C>[C:27]([C:19]1[C:20]2[CH2:25][CH2:24][N:23]([CH2:48][CH2:47][CH2:46][NH:45][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:22][C:21]=2[S:26][C:18]=1[NH:17][C:16](=[O:30])[NH:15][C:12]1[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=1)(=[O:28])[NH2:29]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 4460490tert-butyl N-(3-bromopropyl)carbamate2×HCID 1182698802-[3-(4-Chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide trifluoroacetate

Product 1

HCID 118270017HCID 118270017, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-[3-(4-Chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide trifluoroacetate (0.48 mmol) in anhydrous DMF was treated with triethyl amine (200 μL, 1.43 mmol) and N-Boc-bromopropylamine (114 mg, 0.48 mmol) and the reaction mixture was allowed to stir at room temperature for 14 h. Analytical HPLC showed close to 50% progression. Another 100 μL of triethyl amine and 70 mg of N-Boc-bromopropylamine were added and the reaction mixture was stirred at room temperature. Upon completion (48 h), DMF was removed under vacuo and the resultant crude mixture was diluted with DCM and washed with water (×2). The organic layer was dried (anhydrous Na2SO4) and concentrated to afford an oil which was purified by flash chromatography Isolera system (SiO2 gel as stationary phase, 40 g HP column, dry loading) using DCM-DCM/MeOH (0%-15% MeOH in DCM) to afford the title compound as a light brown solid (144 mg, 60% yield). 1H NMR (300 MHz, dmso-d6) δ 10.95 (s, 1H), 10.18 (s, 1H), 7.55-7.43 (m, 2H), 7.37-7.27 (m, 2H), 6.82 (s, 1H), 3.53-3.43 (m, 2H), 3.03-2.90 (m, 2H), 2.85-2.57 (m, 4H), 2.50-2.40 (m, 2H), 1.69-1.53 (m, 2H), 1.37 (s, 9H). LRMS [M+H]508.

Workup

  1. customAnalytical HPLC showed close to 50% progression
  2. stirringthe reaction mixture was stirred at room temperature
  3. customUpon completion (48 h), DMF was removed under vacuo
  4. additionthe resultant crude mixture was diluted with DCM
  5. washwashed with water (×2)
  6. dry with materialThe organic layer was dried (anhydrous Na2SO4)
  7. concentrationconcentrated
  8. customto afford an oil which
  9. customwas purified by flash chromatography Isolera system (SiO2 gel as stationary phase, 40 g HP column, dry loading)

Sources & evidence

ORD record
ord-b24ff124bd7141128d55be0eca9a874f
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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