Potassium Carbonate → HCID 178481510, compound

HRID 2362475Notes

Reaction equation

HRID 2362475 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:8]2([CH3:24])[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10](=[N:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[NH:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([OH:35])=[C:30](B(O)O)[CH:31]=1.C([O-])([O-])=O.[K+].[K+]>C(COC)OC.C(O)(C)(C)C.[Pd]>[Cl:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:3]=[C:4]([C@:8]3([CH3:24])[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10](=[N:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])[NH:9]3)[CH:5]=[CH:6][CH:7]=2)[C:29]([OH:35])=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)HCID 178481508HCID 178481508, compound

Product 1

HCID 178481510HCID 178481510, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6386tert-ButanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (S)-tert-butyl 4-(3-bromophenyl)-1,4-dimethyl-6-oxo-tetrahydropyrimidin-2(1H)-ylidenecarbamate (CF2; R1=R6=Me) (0.25 g, 0.6 mmol), 5-chloro-2-hydroxyphenylboronic acid (R21=5-chloro-2-hydroxyphenyl; 0.2 g, 1.2 mmol, 2 eq), Fibrecat (4.26% of Pd, 0.7 g) and 1N aq. K2CO3 (0.5 mL) in dimethoxyethane (DME, 10 mL) or tert-butanol (10 mL) in a 20 mL Smith process vial equipped with stir a bar was sealed and heated in an Emrys optimizer at 110° C. for 15 min. After cooling, the reaction mixture was transferred to a pre-packed Si-Carbonate column and eluted with MeOH/CH2Cl2 (1:1). The eluant was collected and concentrated under reduced pressure to give 0.32 g of the crude product as an oil. The crude product was purified by silica gel chromatography (20-50% EtOAc/hexanes gradient) to yield 0.13 g (0.3 mmol, 48%) of (S)-tert-butyl 4-(3-(3-chloro-6-hydroxyphenyl)-phenyl)-1,4-dimethyl-6-oxo-tetrahydropyrimidin-2(1H)-ylidenecarbamate (CF3; R1=R6=Me, R21=3-chloro-6-hydroxyphenyl) as a white solid. 1HNMR (CDCl3, 300 MHz): δ 7.48-4.32 (m, 2H), 7.20 (m, 3H), 6.84 (m, 2H), 5.68 (br s, 1H), 3.28 (d, J=15.7 Hz, 1H), 3.21 (s, 3H), 2.96(d, J=15.3 Hz, 1H), 1.68 (s, 3H), 1.53 (s, 9H). MS (ESI): MH+=443.7, 445.7; M+−56=388.0. HPLC Rt (A)=6.99 min.

Workup

  1. customvial equipped
  2. customwas sealed
  3. temperatureAfter cooling
  4. washeluted with MeOH/CH2Cl2 (1:1)
  5. customThe eluant was collected
  6. concentrationconcentrated under reduced pressure
  7. customto give 0.32 g of the crude product as an oil
  8. customThe crude product was purified by silica gel chromatography (20-50% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-f087cf2d15af443ab846c935275a2e7c
Source dataset
uspto-grants-2014_04
Patent number
US08691831B2

Reaction notes

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