Dichloromethane → tert-butyl (S)-3-(4-(5-bromo-4-methoxypyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate

HRID 1623024Notes

Reaction equation

HRID 1623024 reaction equation
[C:1]([C:5]1[CH:37]=[CH:36][C:8]([C:9]([NH:11][C@@H:12]([CH2:20][C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:38][C:39]1[C:40]([O:46][CH3:47])=[N:41][C:42](I)=[N:43][CH:44]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>C(#N)C.C1COCC1.O.C([O-])(O)=O.[Na+].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]>[Br:38][C:39]1[C:40]([O:46][CH3:47])=[N:41][C:42]([C:24]2[CH:23]=[CH:22][C:21]([CH2:20][C@H:12]([NH:11][C:9](=[O:10])[C:8]3[CH:36]=[CH:37][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:6][CH:7]=3)[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])=[CH:26][CH:25]=2)=[N:43][CH:44]=1

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 848195205-Bromo-2-iodo-4-methoxypyrimidineHCID 86689698tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate

Product 1

HCID 86689697tert-butyl (S)-3-(4-(5-bromo-4-methoxypyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoateYield 60%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

Prepared using General Procedure 10: A mixture of tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate INT-13 (30.0 mg, 0.06 mmol), 5-bromo-2-iodo-4-methoxypyrimidine (22.3 mg, 0.07 mmol), and sodium carbonate (12.5 mg, 0.12 mmol) in acetonitrile (0.80 mL), THF (0.80 mL) and H2O (0.40 mL) was degassed for 10 min. Pd(dppf)Cl2:CH2Cl2 (5 mg, 0.005 mmol) was added and the reaction mixture heated at 110° C. in a microwave for 30 min. Once cooled, the reaction was diluted with NaHCO3 (5 mL), extracted with EA (3×5 mL) and the combined organics dried over MgSO4 and concentrated. The residue was purified by column chromatography (EA/hexanes) to afford 20.0 mg (60%) of tert-butyl (S)-3-(4-(5-bromo-4-methoxypyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate as a white solid. LCMS-ESI (m/z) calculated for C29H34BrN3O4: 568.5; found 514.2 [M-tBu+H]+, tR=11.0 min. (Method 2).

Workup

  1. customPrepared
  2. temperatureOnce cooled
  3. extractionextracted with EA (3×5 mL)
  4. dry with materialthe combined organics dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-52400dc2a0e54c0185108cef214bd48a
Source dataset
uspto-grants-2014_07
Patent number
US08778923B2

Reaction notes

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