Triethylamine → N-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxamide

HRID 1676278Notes

Reaction equation

HRID 1676278 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[C:9]2=[O:16])=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[F:38][C:39]1[CH:40]=[C:41]([CH:43]=[CH:44][C:45]=1[O:46][C:47]1[CH:52]=[CH:51][N:50]=[C:49]2[CH:53]=[CH:54][S:55][C:48]=12)[NH2:42].CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[F:38][C:39]1[CH:40]=[C:41]([NH:42][C:13]([CH:10]2[CH2:11][CH2:12][N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9]2=[O:16])=[O:15])[CH:43]=[CH:44][C:45]=1[O:46][C:47]1[CH:52]=[CH:51][N:50]=[C:49]2[CH:53]=[CH:54][S:55][C:48]=12

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 41820071-(4-Fluorophenyl)-2-oxo-3-pyrrolidinecarboxylic acidHCID 594244303-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 58949427N-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxamideYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxylic acid (38 mg, 0.169 mmol), EDCI (88 mg, 0.461 mmol), and HOBt (62 mg, 0.461 mmol) in DMF (3 ml) was stirred at room temperature for 1 hour. 3-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline (Example 1, Step B; 40 mg, 0.154 mmol) was added followed by Et3N (0.064 mL, 0.461 mmol). After stirring for 2 hours, the reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (3:1=Et2O:EtOAc to 1:3=Et2O:EtOAc) to afford 38 mg (53%) of the desired product. 1H NMR (400 MHz, CD3OD/CDCl3) δ 8.45 (d, 1H), 7.92 (d, 1H), 7.85 (dd, 1H), 7.61 (m, 2H), 7.54 (d, 1H), 7.44 (m, 1H), 7.30 (t, 1H), 7.12 (m, 2H), 6.59 (d, 1H), 3.99 (m, 2H), 3.80 (dd, 1H), 2.67 (m, 1H), 2.52 (m, 1H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −117.6, −128.3. LRMS (ESI pos) m/e 466.1 (M+1).

Workup

  1. washwashed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude material that
  5. customwas purified by silica gel flash column chromatography (3:1=Et2O:EtOAc to 1:3=Et2O:EtOAc)

Sources & evidence

ORD record
ord-d50189549d5a4dd2b33e8b6a00aab253
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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