Sodium Carbonate → HCID 59299295, compound

HRID 474139Notes

Reaction equation

HRID 474139 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][C@@H:9]2[C@H:16]3[CH2:17][N:12]([CH2:13][CH2:14][CH2:15]3)[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[NH:18]1[C:26]2[C:21](=[CH:22][C:23](B(O)O)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[NH:18]1[C:26]2[C:21](=[CH:22][C:23]([C:2]3[CH:3]=[N:4][C:5]([O:8][C@@H:9]4[C@H:16]5[CH2:17][N:12]([CH2:13][CH2:14][CH2:15]5)[CH2:11][CH2:10]4)=[N:6][CH:7]=3)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343615-Indolylboronic acidHCID 66679914HCID 66679914, compound

Product 1

HCID 59299295HCID 59299295, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
90 °C

Procedure

5.19 g (17.4 mmol) of (4S,5R)-4-(5-bromo-pyrimidin-2-yloxy)-1-aza-bicyclo[3.3.1]nonane is dissolved in 200 ml toluene/EtOH 9:1. 5-Indolyl boronic acid (3.47 g, 21.6 mmol), Pd(PPh3)4 (1.04 g, 0.873 mmol) and a soln. of Na2CO3 (7.38 g, 69.6 mmol) in 35 ml H2O is added. The reaction mixture is stirred at 90° C. for 15 h. After cooling to rt the mixture is filtered over hyflo, the filtrate is extracted with water and brine. The aq. layers are reextracted with AcOEt and the combined organic layers are dried over Na2SO4, filtered and the filtrate is evaporated. The resulting crude product is purified by FC (255 g silica gel, eluent AcOEt/MeOH/Et3N 70:27:3) and recrystallization from EtOH to give 3.87 g (67%) (4S,5R)-4-[5-(1H-indol-5-yl)-pyrimidin-2-yloxy]-1-aza-bicyclo[3.3.1]nonane. MS (ES+): m/e=335 (MR+), m.p. 195-199° C.

Workup

  1. temperatureAfter cooling to rt the mixture
  2. filtrationis filtered over hyflo
  3. extractionthe filtrate is extracted with water and brine
  4. dry with materialthe combined organic layers are dried over Na2SO4
  5. filtrationfiltered
  6. customthe filtrate is evaporated
  7. customThe resulting crude product is purified by FC (255 g silica gel, eluent AcOEt/MeOH/Et3N 70:27:3) and recrystallization from EtOH

Sources & evidence

ORD record
ord-e5f96f413ea24b4c81a728c70058342e
Source dataset
uspto-grants-2014_01
Patent number
US08637517B2

Reaction notes

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