Cesium fluoride → HCID 178461591, compound

HRID 522811Notes

Reaction equation

HRID 522811 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][C@H:12]1[CH3:17])[N:7]=[C:6]([Cl:18])[N:5]=2.[F-].[Cs+].[NH:21]1[C:29]2[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[C:24]=2[CH:23]=[CH:22]1>CC#N.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:18][C:6]1[N:5]=[C:4]2[C:9]([N:10]=[C:2]([C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:24]=3[CH:23]=[CH:22][NH:21]4)[NH:3]2)=[C:8]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][C@H:12]2[CH3:17])[N:7]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27631731H-Indole-4-boronic acidHCID 178461590HCID 178461590, compound

Product 1

HCID 178461591HCID 178461591, compoundYield 63.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

In a sealed tube, to a solution of 8-bromo-2-chloro-6-((R)-3-methyl-morpholin-4-yl)-9H-purine (495 mg, 1.49 mmol) in CH3CN/H2O (11/1.1 mL) was added cesium fluoride (452 mg, 2.98 mmol), indole-4-boronic acid (266 mg, 1.64 mmol), and tetrakis(triphenylphosphine)palladium (172 mg, 0.15 mmol). Then the reaction was conducted under microwave irradiation at 160° C. for 30 min. The solvents were removed under reduced pressure and the crude was purified by flash column chromatography (20-100% EtOAc/cyclohexane gradient) to provide 2-chloro-8-(1H-indol-4-yl)-6-((R)-3-methyl-morpholin-4-yl)-9H-purine (350 mg, 63.8%) as a pale yellow solid. LC-MS at 254 nm; [M+H] 369.2; Rt 1.00 min; (LCMS method 1). (400 MHz, DMSO-d6): 13.59 (s, 1H), 11.41 (s, 1H), 7.73 (dd, 1H), 7.58-7.49 (m, 2H), 7.38-7.20 (m, 2H), 5.14 (s, 1H), 4.05-4.01 (m, 1H), 3.79-3.88 (m, 1H), 3.69-3.79 (m, 1H), 3.57 (s, 1H), 3.60 (s, 1H), 1.41 (d, 3H)

Workup

  1. customThen the reaction was conducted under microwave irradiation at 160° C. for 30 min
  2. customThe solvents were removed under reduced pressure
  3. customthe crude was purified by flash column chromatography (20-100% EtOAc/cyclohexane gradient)

Sources & evidence

ORD record
ord-8a0e7147cb424cbc9476154761e0cab5
Source dataset
uspto-grants-2016_05
Patent number
US09334271B2

Reaction notes

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