Triethylamine → N-(4-fluorophenyl)-N'-(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide

HRID 1011294Notes

Reaction equation

HRID 1011294 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]2=[N:12][CH:13]=[N:14][C:15]([O:16][C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=3)=[C:10]2[CH:9]=[N:8]1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([C:34]2([C:37](O)=[O:38])[CH2:36][CH2:35]2)=[O:33])=[CH:27][CH:26]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(OCC)(=O)C.CN(C=O)C>[F:24][C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:32]([C:34]2([C:37]([NH:23][C:20]3[CH:21]=[CH:22][C:17]([O:16][C:15]4[N:14]=[CH:13][N:12]=[C:11]5[N:7]([CH:2]6[CH2:3][CH2:4][CH2:5][CH2:6][O:1]6)[N:8]=[CH:9][C:10]=45)=[CH:18][CH:19]=3)=[O:38])[CH2:36][CH2:35]2)=[O:33])=[CH:29][CH:30]=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 589380164-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine

Product 1

HCID 11699227N-(4-fluorophenyl)-N'-(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamideYield 95.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine (0.199 g, 0.63 mmol, 1.0 eq.), 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (0.213 g, 0.95 mmol, 1.5 eq), HATU (0.607 g, 1.6 mmol, 2.5 eq), triethylamine (0.26 ml, 1.9 mmol, 3 eq), and anhydrous DMF (5 ml). The mixture was stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate, washed with (2×) H2O (50 ml), sat'd NaHCO3 (2×), 5% LiCl (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo to give N-(4-fluorophenyl)-N′-(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide as a white solid (0.312 g, 95% yield). 1H NMR (400 MHz, CDCl3): 9.21 (s, 1H), 8.82 (bs, 1H), 8.56 (s, 1H), 7.96 (s, 2H), 7.65 (dd, 2H), 7.48 (m, 2H), 7.21 (m, 2H), 7.05 (t, 2H), 6.05 (dd, 1H), 3.78 (m, 1H), 2.61 (m, 1H), 2.16 (m, 1H), 2.14 (s,1H), 1.99 (m, 1H), 1.81 (m, 2H), 1.69 (m, 4H), 1.60 (s, 1H); MS (ESI) for C27H25FN7O4: 517 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. washwashed with (2×) H2O (50 ml), sat'd NaHCO3 (2×), 5% LiCl (3×), sat'd NaCl (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f7210529da814dbfab681e409d02aa4e
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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