Sodium Carbonate → HCID 178429382, compound

HRID 707318Notes

Reaction equation

HRID 707318 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C@H:9]2[CH2:12][C@H:11]([N:13]3[C:17]4=[N:18][CH:19]=[CH:20][CH:21]=[C:16]4[C:15]([CH3:23])([CH3:22])[C:14]3=[O:24])[CH2:10]2)=[N:6][CH:7]=1.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:25]1([C:2]2[CH:3]=[N:4][C:5]([NH:8][C@H:9]3[CH2:12][C@H:11]([N:13]4[C:17]5=[N:18][CH:19]=[CH:20][CH:21]=[C:16]5[C:15]([CH3:23])([CH3:22])[C:14]4=[O:24])[CH2:10]3)=[N:6][CH:7]=2)[CH2:27][CH2:26]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 178429381HCID 178429381, compound

Product 1

HCID 178429382HCID 178429382, compound

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

1-(Trans-3-((5-bromopyrimidin-2-yl)amino)cyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (example 60, 95 mg, 0.245 mmol), cyclopropyl boronic acid (31.5 mg, 0.367 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (17.33 mg, 0.024 mmol) were mixed in 1,4-dioxane (1 msL) under an argon atmosphere. Aqueous sodium carbonate (2 M, 0.367 mL, 0.734 mmol) was added via syringe and the reaction mixture was stirred at 80° C. for 18 hrs. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated to dryness under reduced pressure. The resulting crude product was purified via silica gel flash column chromatography eluting with 0 to 100% ethyl acetate in hexanes to yield 1-(trans-3-((5-cyclopropylpyrimidin-2-yl)amino)cyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one as a light yellow solid. M+1: 350.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.59-0.66 (m, 2 H) 0.78-0.94 (m, 2 H) 1.31 (s, 6 H) 1.75 (tt, J=8.44, 5.16 Hz, 1 H) 2.25-2.37 (m, 2 H) 3.18 (m, 2 H) 4.47-4.57 (m, 1 H) 5.16 (quin, J=8.41 Hz, 1 H) 7.07 (dd, J=7.24, 5.28 Hz, 1 H) 7.51 (br. d, J=6.50 Hz, 1 H) 7.76 (dd, J=7.24, 1.56 Hz, 1 H) 8.12 (s, 2 H) 8.21 (dd, J=5.28, 1.56 Hz, 1 H).

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. customThe resulting crude product was purified via silica gel flash column chromatography
  7. washeluting with 0 to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-87a8fd872de1401bb8c519522971b97a
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

Loading…