2-Methoxyphenethylamine → N1-(3-Fluoro-4-(2-(3-methoxy-4-(2-morpholinoethoxy)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N2-(2-methoxyphenethyl)oxalamide

HRID 2193713Notes

Reaction equation

HRID 2193713 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:35][C:36](=[O:42])[C:37](OCC)=[O:38])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:20]([O:33][CH3:34])[CH:19]=3)[S:17][C:10]=12.[CH3:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[CH2:51][CH2:52][NH2:53]>>[F:1][C:2]1[CH:3]=[C:4]([NH:35][C:36](=[O:42])[C:37]([NH:53][CH2:52][CH2:51][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[O:44][CH3:43])=[O:38])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:20]([O:33][CH3:34])[CH:19]=3)[S:17][C:10]=12

Participants

3

Reactant 2

HCID 748962-MethoxyphenethylamineHCID 58790158Ethyl 2-(3-Fluoro-4-(2-(3-methoxy-4-(2-morpholinoethoxy)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)-2-oxoacetate

Product 1

HCID 16042167N1-(3-Fluoro-4-(2-(3-methoxy-4-(2-morpholinoethoxy)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N2-(2-methoxyphenethyl)oxalamideYield 57.1%

Procedure

Amino ester 140 (80 mg, 0.13 mmol) and 2-(2-methoxyphenyl)ethanamine (0.2 mL, 1.34 mmol) were mixed together and stirred at room temperature until completion of the reaction. The mixture was quenched with a saturated aqueous solution of ammonium chloride and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and evaporated. The crude product was purified by flash chromatography (eluent: 3% MeOH/97% DCM to 5% MeOH/95% DCM). This solid product was then triturated with ethyl acetate to afford pure title compound 136 as a white solid (52 mg, 57% yield). 1H NMR (DMSO-d6) δ (ppm): 11.03 (s, 1H), 9.04 (t, J=5.9 Hz, 1H), 8.48 (d, J=5.5 Hz, 1H), 8.05-8.01 (m, 2H), 7.82 (d, J=9.0 Hz, 1H), 7.53 (t, J=9.1 Hz, 1H), 7.47 (d, J=2.2 Hz, 1H), 7.38 (dd, J=2.2 and 8.2 Hz, 1H), 7.21 (td, J=1.8 and 7.8 Hz, 1H), 7.14 (dd, J=1.8 and 7.4 Hz, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.97 (d, J=7.4 Hz, 1H), 6.88 (td, J=1.0 and 7.3 Hz, 1H), 6.60 (d, J=5.5 Hz, 1H), 4.14 (t, J=6.0 Hz, 2H), 3.89 (s, 3H), 3.80 (s, 3H), 3.59-3.57 (m, 4H), 3.46-3.41 (m, 2H), 2.83 (t, J=7.0 Hz, 2H), 2.73-2.70 (m, 2H), one peak (4H) did not show, it was probably under H2O or DMSO. MS (m/z): 701.1 (M+H).

Workup

  1. customThe mixture was quenched with a saturated aqueous solution of ammonium chloride
  2. extractionextracted three times with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash chromatography (eluent: 3% MeOH/97% DCM to 5% MeOH/95% DCM)
  8. customThis solid product was then triturated with ethyl acetate

Sources & evidence

ORD record
ord-e7171ef43cb74133a1acd0b671e95223
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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