Water → HCID 86696729, compound

HRID 2365875Notes

Reaction equation

HRID 2365875 reaction equation
CC([O-])(C)C.[K+].[Si]([O:14][CH2:15][CH:16]([C:22]1[N:23]([C:31]([O:33]C(C)(C)C)=[O:32])[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2)OS(C)(=O)=O)(C(C)(C)C)(C)C.[O:38]1[CH2:43][CH2:42][CH:41]([NH:44][C:45]2[N:50]=[C:49]([C:51]3[CH:56]=[CH:55][NH:54][C:53](=[O:57])[CH:52]=3)[CH:48]=[CH:47][N:46]=2)[CH2:40][CH2:39]1.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.C(Cl)Cl>[CH:31]([OH:33])=[O:32].[OH:14][CH2:15][CH:16]([N:54]1[CH:55]=[CH:56][C:51]([C:49]2[CH:48]=[CH:47][N:46]=[C:45]([NH:44][CH:41]3[CH2:40][CH2:39][O:38][CH2:43][CH2:42]3)[N:50]=2)=[CH:52][C:53]1=[O:57])[C:22]1[NH:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2

Participants

8

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 86696649HCID 86696649, compoundHCID 86696730HCID 86696730, compound

Product 1

HCID 86696729HCID 86696729, compoundYield 1.9%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
95 °C

Procedure

Potassium 2-methylpropan-2-olate (114 mg, 1.02 mmol), tetrabutylammonium iodide (57 mg, 0.15 mmol), and a solution of tert-butyl 2-(2-(tert-butyldimethylsilyloxy)-1-methylsulfonyloxyethyl)-1H-indole-1-carboxylate (0.61 mmol) in anhydrous THF (15 mL) were added to a suspension of 4-(2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (139 mg, 0.510 mmol) in anhydrous THF (5.0 mL). The resulting mixture was stirred at 95° C. under microwave irradiation for 2 hours. The reaction mixture was then treated with water (20 mL) and diluted with DCM. After removal of the insoluble by filtration, the filtrate was extracted with DCM. The combined organic phase was dried over Na2SO4 and concentrated. The residue was purified with prep-HPLC to afford 1-(2-hydroxy-1-(1H-indol-2-yl)ethyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one formate (4.6 mg, 1.1% yield) as a solid. 1H NMR (500 MHz, (CD3)2SO) δ 11.20 (s, 1H), 8.46-8.40 (m, 2H), 7.64 (d, J=7.0 Hz, 1H), 7.50 (d, J=8.5 Hz, 1H), 7.35-7.31 (m, 2H), 7.14-7.12 (m, 2H), 7.06 (m, 1H), 6.97 (m, 1H), 6.81 (d, J=7.0 Hz, 1H), 6.54 (s, 1H), 6.24 (m, 1H), 5.30 (m, 1H), 4.13-4.07 (m, 2H), 3.97 (m, 1H), 3.88-3.86 (m, 2H), 3.41-3.36 (m, 2H), 1.85-1.83 (m, 2H), 1.56-1.49 (m, 2H); LCMS (ESI) m/z: 432.2 [M+H]+.

Workup

  1. customAfter removal of the
  2. filtrationinsoluble by filtration
  3. extractionthe filtrate was extracted with DCM
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified with prep-HPLC

Sources & evidence

ORD record
ord-7b72432501b34c15a794dcba37342ecd
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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