Water → HCID 86696729, compound

HRID 1774229Notes

Reaction equation

HRID 1774229 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-methyl sulfonyloxyethyl)-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-e4b63e7e46024ac3b8dc82742da1f358
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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