Potassium Carbonate → (4-(6-Amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl ester

HRID 1522103Notes

Reaction equation

HRID 1522103 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]2[C:18](Cl)=[C:17]([NH2:20])[N:16]=[CH:15][N:14]=2)=[CH:8][CH:7]=1)[CH3:2].[O:22]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]2[C:18]([C:32]3[CH:33]=[CH:34][C:29]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:30][CH:31]=3)=[C:17]([NH2:20])[N:16]=[CH:15][N:14]=2)=[CH:8][CH:7]=1)[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 71092849(4-(6-Amino-5-chloro-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl ester

Product 1

HCID 71092830(4-(6-Amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl esterYield 94.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a microwave vial was placed [4-(6-amino-5-chloro-pyrimidin-4-ylamino)-phenyl]-acetic acid ethyl ester (1.4 g; 3.423 mmol; 1.0 eq.), (4-phenoxyphenyl)boronic acid (1598.9 mg; 7.470 mmol; 2.18 eq.), palladium acetate (38.4 mg; 0.171 mmol; 0.1 eq.), dicyclohexyl-(2′,6′-dimethoxy-biphenyl-2-yl)-phosphane (140.5 mg; 0.342 mmol; 0.1 eq.), potassium carbonate (1419.2 mg; 10.269 mmol; 3.0 eq.) suspended in dioxane (15.0 ml) and water (1.5 ml). The vial was flushed with nitrogen. The reaction vial was run in a microwave for 3 hours at 150° C. The mixture was filtered, quenched in water and extracted with EtOAc (3×). The combined organic layer were dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified using Biotage column chromatography (50/50% Hexanes/EtOAc to 100% EtOAc). Fractions containing the desired product were collected and concentrated to afford (4-(6-amino-5-(4-phenoxyphenyl)-pyrimidin-4-ylamino)-phenyl)-acetic acid ethyl ester (1.43 g, 90% yield) as a yellow foam. MS: m/z=441 [M+H]+. 1H-NMR (DMSO-d6) δ 8.06 (s, 1H), 7.45 (t, 4H), 7.34 (d, 2H), 7.16 (dd, 8H), 5.77 (bs, 2H), 4.10 (q, 2H), 3.56 (s, 2H), 1.20 (t, 3H).

Workup

  1. customThe vial was flushed with nitrogen
  2. customThe reaction
  3. filtrationThe mixture was filtered
  4. customquenched in water
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic layer were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude compound was purified
  10. additionFractions containing the desired product
  11. customwere collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-91b5aff758d44cf7bde6926f9bedfbee
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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