Propylphosphonic anhydride → N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)ace tamide

HRID 1050197Notes

Reaction equation

HRID 1050197 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=O)=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[CH3:31][N:32]([CH3:47])[CH2:33][CH2:34][O:35][C:36]1[CH:37]=[C:38]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[NH2:39].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>N1C=CC=CC=1>[CH3:31][N:32]([CH3:47])[CH2:33][CH2:34][O:35][C:36]1[CH:37]=[C:38]([NH:39][C:27](=[O:29])[CH2:26][C:23]2[CH:24]=[CH:25][C:20]([C:6]3[CH:7]=[N:8][C:9]([O:10][CH2:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=4)=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=3)=[CH:21][C:22]=2[F:30])[CH:40]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:42]=1

Participants

5

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 210495493-[2-(Dimethylamino)ethoxy]-5-(trifluoromethyl)anilineHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acid

Product 1

HCID 90422426N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)ace tamideYield 64.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
27 °C

Procedure

To a solution of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (100 mg, 0.243 mmol) and 3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)aniline (60.3 mg, 0.243 mmol) in pyridine (2 mL) was added T3P® (0.5 mL, 0.243 mmol) at 27° C. under N2. The mixture was stirred at 27° C. for 30 min. LCMS showed the reaction was completed. Then the mixture was put onto ice (10 mg). The precipitate was filtered and redissolved in DCM (5 mL). The solution was washed with water (5 mL×2), and the combined organic extracts were dried over Na2SO4, filtered and concentrated. The residue was suspended in PE/EA (2:1, v/v, 8 mL) and stirred for 10 min. The solid was filtered, and washed with PE/EA (2:1, v/v, 10 mL) and dried in vacuo to give an off-white solid of N-(3-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (100 mg, 0.156 mmol, 64.1% yield). TLC (PE/EA=1:1, Rf=0.3): 1H NMR (400 MHz, CD3OD) δ 7.97-7.92 (m, 1H), 7.76 (br. s., 1H), 7.48-7.37 (m, 7H), 7.04 (s, 1H), 6.91 (d, J=8.6 Hz, 2H), 5.36 (s, 2H), 4.14 (q, J=7.1 Hz, 4H), 3.86-3.78 (m, 5H), 2.97 (br. s., 8H), 1.42 (t, J=6.9 Hz, 4H). ES-LCMS m/z 642 (M+H).

Workup

  1. filtrationThe precipitate was filtered
  2. dissolutionredissolved in DCM (5 mL)
  3. washThe solution was washed with water (5 mL×2)
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. stirringstirred for 10 min
  8. filtrationThe solid was filtered
  9. washwashed with PE/EA (2:1, v/v, 10 mL)
  10. customdried in vacuo

Sources & evidence

ORD record
ord-26f9f89df3e74d4eade1d2082f1238b3
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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