Triethylamine → N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]-cyclopropane-1,1-dicarboxamide

HRID 1011290Notes

Reaction equation

HRID 1011290 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.[F:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([C:29]2([C:32](O)=[O:33])[CH2:31][CH2:30]2)=[O:28])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>O.CN(C=O)C>[F:19][C:20]1[CH:21]=[CH:22][C:23]([NH:26][C:27]([C:29]2([C:32]([NH:18][C:4]3[CH:5]=[CH:6][C:7]([O:8][C:9]4[C:10]5[CH:17]=[CH:16][NH:15][C:11]=5[N:12]=[CH:13][N:14]=4)=[C:2]([F:1])[CH:3]=3)=[O:33])[CH2:31][CH2:30]2)=[O:28])=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 589380223-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-phenylamine

Product 1

HCID 11698079N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]-cyclopropane-1,1-dicarboxamideYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 (0.07 g, 0.29 mmol, 1.0 eq.), 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (0.105 g, 0.32 mmol), HATU (0.304 g, 0.58 mmol), triethylamine (0.13 ml, 0.87 mmol), and anhydrous DMF (3 ml). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with H2O (50 ml) and extracted with CHCl3 (3×). The combined CHCl3 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]-cyclopropane-1,1-dicarboxamide as a white solid (0.011 g, 9.0% yield). 1H NMR (400 MHz, DMSO): 9.59 (bs, 1H), 8.47 (s, 1H), 7.85 (m, 2H), 7.65 (m, 3H), 7.48 (d, 1H), 7.36 (t, 1H), 7.19 (d, 1H), 7.15 (t, 3H), 1.44 (s, 5H); MS (ESI) for C23H17F2N5O3: 450 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. extractionextracted with CHCl3 (3×)
  3. extractionThe combined CHCl3 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-9b58b1e862ff4d9dbf5a30d4c53e0e4e
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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