Water → 4-[6-{[(1r,3s,4s)-3-{[Tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-8-yl]-7-chloroquinoline

HRID 1747681Notes

Reaction equation

HRID 1747681 reaction equation
[Si:1]([O:8][C@@H:9]1[C@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:12][C@@H:11]([O:23][C:24]2[N:32]=[CH:31][N:30]=[C:29]3[C:25]=2[N:26]=[C:27](I)[N:28]3[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].COCCOC.[Cl:46][C:47]1[CH:56]=[C:55]2[C:50]([C:51](B3OC(C)(C)C(C)(C)O3)=[CH:52][CH:53]=[N:54]2)=[CH:49][CH:48]=1.[OH-].[Ba+2].[OH-].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>[Si:1]([O:8][C@@H:9]1[C@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:12][C@@H:11]([O:23][C:24]2[N:32]=[CH:31][N:30]=[C:29]3[C:25]=2[N:26]=[C:27]([C:51]2[C:50]4[C:55](=[CH:56][C:47]([Cl:46])=[CH:48][CH:49]=4)[N:54]=[CH:53][CH:52]=2)[N:28]3[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 6093286Barium hydroxideHCID 162180767-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 667979406-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 667979204-[6-{[(1r,3s,4s)-3-{[Tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-8-yl]-7-chloroquinoline

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl) silyl]oxy}methyl)cyclopentyl]oxy}-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (258.4 mg, 0.0003752 mol) in 1,2-Dimethoxyethane (3.0 mL, 0.029 mol) was added 7-chloroquinoline-4-boronic acid pinacol ester (0.158 g, 0.000546 mol), barium hydroxide (0.228 g, 0.00133 mol), water (0.5 mL, 0.03 mol) and Tetrakis(triphenylphosphine)palladium(0) (0.02 g, 0.00002 mol), and the mixture was heated at 90° C. overnight. The reaction was cooled, quenched by addition of water and the mixture was extracted with DCM (3×), washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 30% EtOAc/hexanes) to obtain 180 mg (66.2%) mg. Reference: Cammidge, A. N.; Crepy, K. V. L. Tetrahedron, 2004, 60, 4377-4386.

Workup

  1. temperatureThe reaction was cooled
  2. customquenched by addition of water
  3. extractionthe mixture was extracted with DCM (3×)
  4. washwashed with water, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (0 to 30% EtOAc/hexanes)
  9. customto obtain 180 mg (66.2%) mg

Sources & evidence

ORD record
ord-1d4201a9d4a040fe8a769f668a799426
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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