Water → N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]propanediamide

HRID 1011289Notes

Reaction equation

HRID 1011289 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:18])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:10]2[CH:17]=[CH:16][NH:15][C:11]=2[N:12]=[CH:13][N:14]=1.CN(C(ON1N=N[C:29]2[CH:30]=[CH:31][CH:32]=N[C:28]1=2)=[N+](C)C)C.[F:36][P-](F)(F)(F)(F)F.C(N([CH2:48][CH3:49])CC)C.[CH3:50][N:51]([CH:53]=[O:54])C.[OH2:55]>>[F:36][C:30]1[CH:31]=[CH:32][C:50]([NH:51][C:53](=[O:54])[CH2:48][C:49]([NH:18][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[C:10]4[CH:17]=[CH:16][NH:15][C:11]=4[N:12]=[CH:13][N:14]=3)=[C:2]([F:1])[CH:3]=2)=[O:55])=[CH:28][CH:29]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 589380223-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-phenylamine

Product 1

HCID 11568014N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]propanediamideYield 21%

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-phenylamine (0.141 mg, 0.57 mmol, 1.0 eq.), 1-(4-fluoro-phenylcarbamoyl)-carboxylic acid (0.193 g, 0.88 mmol), HATU (0.584 g, 1.14 mmol), triethylamine (0.23 ml, 1.3 mmol) and anhydrous DMF (5 ml). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with H2O (100 ml) and extracted with CHCl3 (3×). The combined organic extractions were washed with H2O (1×), sat'd NaHCO3 (2×), 10% LiCl (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The resulting crude residue was purified by HPLC to yield N-(4-fluorophenyl)-N′-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]propanediamide as a white solid (0.051 g, 21% yield). 1H NMR (400 MHz, DMSO): 12.30 (s, 1H), 10.49 (s, 1H), 10.28 (s, 1H), 8.29(s, 1H), 7.80 (dd, 1H), 7.65 (m, 2H), 7.51 (m, 1H), 7.40 (m, 2H), 7.19 (m, 2H), 6.58 (d, 1H), 3.49 (s, 2H); MS (ESI) for C21H15F2N5O3: 424 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. extractionextracted with CHCl3 (3×)
  3. extractionThe combined organic extractions
  4. washwere washed with H2O (1×), sat'd NaHCO3 (2×), 10% LiCl (3×), sat'd NaCl (1×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude residue was purified by HPLC

Sources & evidence

ORD record
ord-e843c13aa865475c886b3bcfbf0dead6
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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