Hydantoin → 3-{2-[(4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)oxy]ethyl}imidazolidine-2,4-dione

HRID 550500Notes

Reaction equation

HRID 550500 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[NH:23][N:24]=[C:25]([O:26][CH2:27][CH2:28]O)[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[NH:30]1[CH2:36][C:34](=[O:35])[NH:33][C:31]1=[O:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[NH:23][N:24]=[C:25]([O:26][CH2:27][CH2:28][N:33]4[C:34](=[O:35])[CH2:36][NH:30][C:31]4=[O:32])[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 10006HydantoinHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 116759782-[(4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)oxy]ethanol

Product 1

HCID 116273753-{2-[(4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)oxy]ethyl}imidazolidine-2,4-dioneYield 25.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-[(4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)oxy]ethanol (prepared as described in Example 4/50 mg, 0.12 mmol), hydantoin (36 mg, 0.36 mmol) and triphenylphosphine (94 mg) were dissolved in a 1:1 mixture of THF and DMF (1.2 ml). Ditertbutyl azodicarboxylate (69 mg, 0.3 mmol) was added at 0° C. and mixture was stirred at room temperature for 3 hours. After evaporation, the crude mixture was purified by preparative HPLC (column beta-basic, Hypercil 5 μm, 21×100 mm) eluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient) to give the title compound (15 mg, 25%); NMR Spectrum: 3.88 (t, 2H), 3.96 (s, 2H), 4.37 (t, 2H), 5.29 (s, 2H), 7.24 (d, 1H), 7.36-7.38 (m, 1H), 7.58 (d, 1H), 7.78 (dd, 1H), 7.88 (t, 1H), 8.09 (s, 1H), 8.17 (s, 1H), 8.21 (s, 1H), 8.34 (s, 1H), 8.59 (d, 1H); Mass Spectrum: 495 (MH+).

Workup

  1. customAfter evaporation
  2. customthe crude mixture was purified by preparative HPLC (column beta-basic, Hypercil 5 μm, 21×100 mm)
  3. washeluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient)

Sources & evidence

ORD record
ord-34485431451e4e449567669071a4ddda
Source dataset
uspto-grants-2011_05
Patent number
US07947676B2

Reaction notes

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