Water → HCID 11699228, compound

HRID 1011306Notes

Reaction equation

HRID 1011306 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:15]=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][C:12]=2[O:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=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.O>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:12]4[N:11]=[CH:10][N:9]=[C:8]5[C:13]=4[N:14]=[CH:15][N:7]5[CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)=[CH:18][CH:19]=3)=[O:38])[CH2:36][CH2:35]2)=[O:33])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 962WaterHCID 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 58938018HCID 58938018, compound

Product 1

HCID 11699228HCID 11699228, compoundYield 83.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yloxy]-phenylamine (0.311 g, 1 mmol) and 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (0.334 g, 1.5 mmol) in DMF (5 mL) was added TEA (216 μL, 2 mmol) followed by HATU (0.76 g, 2 mmol). The resulting solution was stirred overnight at room temperature. The reaction mixture was dumped into water (25 mL) and extracted with EtOAc (2×). The combined organic extracts were washed with 10% LiCl(aq.) (4×), satd. NaHCO3(aq) (2×), water, (1×) and brine (1×), followed by drying over MgSO4 and concentration in vacuo. The crude solids were purified by flash chromatography (silica gel, 1:1 EtOAc:Hexanes containing 2% 7N NH3 in MeOH), affording N-(4-fluorophenyl)-N′-(4-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide (0.430 g, 83% yield) as a solid. 1H NMR (400 MHz, CDCl3): δ 9.50 (s, 1H), 8.95 (s, 1H), 8.45 (s, 1H), 7.60 (m, 2H), 7.45 (m, 2H), 7.20 (m, 2H), 7.0 (m, 2H), 5.8 (m, 1H), 4.20 (m, 1H), 3.8 (m, 1H), 2.20 (m, 3H), 1.80 (m, 2H), 1.7 (m, 5H). MS (ESI) for C27H25FN6O4: 517 (MH+).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic extracts were washed with 10% LiCl(aq.) (4×)
  3. dry with materialby drying over MgSO4 and concentration in vacuo
  4. customThe crude solids were purified by flash chromatography (silica gel, 1:1 EtOAc:Hexanes containing 2% 7N NH3 in MeOH)

Sources & evidence

ORD record
ord-8236981c64504dc3b020f31e498613b6
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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