Lithium Chloride → 5-(4-(benzyloxy)-3-fluorophenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 1676335Notes

Reaction equation

HRID 1676335 reaction equation
Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][C:26]=1[F:34])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:27][C:26]=1[F:34])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 673454265-bromo-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 673485585-(4-(benzyloxy)-3-fluorophenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-oneYield 64%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-bromo-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.145 g, 0.518 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.153 g, 0.621 mmol), Pd(PPh3)4 (0.030 g, 0.026 mmol) and lithium chloride (0.110 g, 2.59 mmol) in dioxane (1.5 mL) and 2M aqueous Na2CO3 (1.5 mL) was stirred at 100° C. for 20 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude black solid. The crude product was purified by flash column chromatography, eluting with 10:1 dichloromethane/EtOAc. The desired product (0.133 g, 64%) was obtained as an off-white waxy solid. 1H NMR (400 MHz, DMSO-d6) δ 8.90 (br s, 1H), 7.93 (s, 1H), 7.59 (dd, J=1.95, 13.7 Hz, 1H), 7.55-7.31 (m, 10H), 7.22 (t, J=9.0 Hz, 1H), 7.14 (t, J=7.4 Hz, 1H), 5.20 (s, 2H), 3.55 (s, 3H). LRMS (ESI pos) m/e 402 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude black solid
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with 10:1 dichloromethane/EtOAc

Sources & evidence

ORD record
ord-eb8375a9c8874d9bbc66ff2dd677f1ca
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…