Potassium Phosphate, Tribasic → Methyl 2-(4-(4-(2-aminopyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

HRID 881721Notes

Reaction equation

HRID 881721 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]34[CH2:22][CH2:21][C:18]([CH2:23][C:24]([O:26][CH3:27])=[O:25])([CH2:19][CH2:20]3)[O:17][CH2:16]4)=[CH:11][CH:10]=2)O1.Br[C:30]1[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C(COC)OC>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:9]2[CH:10]=[CH:11][C:12]([C:15]34[CH2:22][CH2:21][C:18]([CH2:23][C:24]([O:26][CH3:27])=[O:25])([CH2:19][CH2:20]3)[O:17][CH2:16]4)=[CH:13][CH:14]=2)=[CH:31][N:32]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2313102-Amino-5-bromopyrimidineHCID 86700826Methyl 2-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

Product 1

HCID 86700829Methyl 2-(4-(4-(2-aminopyrimidin-5-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetateYield 105%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a reaction vial containing methyl 2-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (200 mg, 0.52 mmol), 5-bromopyrimidin-2-amine (108 mg, 0.62 mmol) and K3PO4 (132 mg, 0.62 mmol) was added dimethoxyethane (4.8 ml). The mixture was stirred at room temperature and degassed after the addition of EtOH (1.6 ml) and water (0.64 ml). PdCl2(dppf) DCM adduct (21 mg, 0.03 mmol) was added and the mixture was heated to 8° C. in an oil bath for 3 hours. The reaction mixture was then concentrated to dryness and taken up in DCM. The slurry was dried over sodium sulfate and filtered through a pad of celite. The filtrate was concentrated and purified by column chromatography to afford the title compound (193 mg, 84% yield). LC/MS, ESI-MS(+): 354.3, RT: 1.06 (Condition E).

Workup

  1. customdegassed
  2. additionafter the addition of EtOH (1.6 ml) and water (0.64 ml)
  3. temperaturethe mixture was heated to 8° C. in an oil bath for 3 hours
  4. concentrationThe reaction mixture was then concentrated to dryness
  5. dry with materialThe slurry was dried over sodium sulfate
  6. filtrationfiltered through a pad of celite
  7. concentrationThe filtrate was concentrated
  8. custompurified by column chromatography

Sources & evidence

ORD record
ord-d12e49ad3c3f44db926dc759c7afa167
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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