Tetrabutylammonium Fluoride → N-(4-(6-((2-morpholinoethyl)carbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1011303Notes

Reaction equation

HRID 1011303 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:25]5[CH:32]=[C:31]([C:33](=[O:43])[NH:34][CH2:35][CH2:36][N:37]6[CH2:42][CH2:41][O:40][CH2:39][CH2:38]6)[N:30](COCC[Si](C)(C)C)[C:26]=5[N:27]=[CH:28][N:29]=4)=[C:19]([F:52])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[F:52][C:19]1[CH:18]=[C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[O:10])[CH2:12][CH2:13]2)=[O:15])[CH:22]=[CH:21][C:20]=1[O:23][C:24]1[C:25]2[CH:32]=[C:31]([C:33]([NH:34][CH2:35][CH2:36][N:37]3[CH2:38][CH2:39][O:40][CH2:41][CH2:42]3)=[O:43])[NH:30][C:26]=2[N:27]=[CH:28][N:29]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58938029cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[6-(2-morpholin-4-yl-ethylcarbamoyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amide

Product 1

HCID 11585247N-(4-(6-((2-morpholinoethyl)carbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 35%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask equipped with a magnetic stir bar was added cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[6-(2-morpholin-4-yl-ethylcarbamoyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amide (0.049 g, 0.07 mmol, 1.0 eq.) and a 1M tetrabutylammonium fluoride solution (5 ml). The reaction was heated to reflux for 1 hour. The reaction was diluted with ethyl acetate, and was washed with (2×) H2O (50 ml), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography using 3% methanol and DCM as the eluent, giving N-{3-fluoro-4-[(6-{[(2-morpholin-4-ylethyl)amino]carbonyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide as a white solid (0.014 g, 35% yield). 1H NMR (400 MHz, DMSO): 12.92 (s, 1H), 10.39 (bs, 1H), 10.36 (s, 1H), 10.04 (s, 1H), 9.11 (m, 1H), 8.37 (s, 1H), 7.83 (d, 1H), 7.66 (m, 2H), 7.46 (m, 1H), 7.40 (m, 1H), 7.15 (t, 2H), 3.98 (d, 2H), 3.77 (m, 3H), 3.56 (d, 2H), 3.16 (m, 2H), 3.02 (m, 3H), 1.59 (m, 2H), 1.36 (m, 2H); MS (ESI) for C30H29F2N7O5: 606 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 1 hour
  4. washwas washed with (2×) H2O (50 ml), sat'd NaCl (1×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-3e4649e2854145fda85b2a35c6d04663
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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