5-Bromo-2-iodopyrimidine → tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate

HRID 1775830Notes

Reaction equation

HRID 1775830 reaction equation
[C:1]([C:5]1[CH:33]=[CH:32][C:8]([C:9]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20](B3OC(C)(C)C(C)(C)O3)=[CH:19][CH:18]=2)[C:13]([O-:15])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:34][C:35]1[CH:36]=[N:37][C:38](I)=[N:39][CH:40]=1>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(#N)C.C1COCC1.O>[Br:34][C:35]1[CH:36]=[N:37][C:38]([C:20]2[CH:19]=[CH:18][C:17]([CH2:16][C@H:12]([NH:11][C:9](=[O:10])[C:8]3[CH:32]=[CH:33][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:6][CH:7]=3)[C:13]([O:15][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:14])=[CH:22][CH:21]=2)=[N:39][CH:40]=1

Participants

5

Reactant 2

HCID 70066515-Bromo-2-iodopyrimidineHCID 86689677(S)-2-(4-(tert-butyl)benzamido)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate

Product 1

HCID 86689676tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoateYield 58%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18694733Acetonitrile tetrahydrofuran waterSolvent

Conditions

Temperature
110 °C

Procedure

Prepared using General Procedure 10. Into a degassed solution of (S)-2-(4-(tert-butyl)benzamido)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate INT-13 (1.0 g, 2.0 mmol), Na2HCO3 (420 mg, 3.9 mmol), and 5-bromo-2-iodopyrimidine (615 mg, 2.2 mmol) in 2/2/1 ACN/THF/H2O was added Pd(dppf)Cl2 (140 mg, 0.2 mmol). The reaction mixture was heated at 110° C. for 1 h in a microwave reactor. The reaction mixture was concentrated, dissolved in DCM and washed with H2O. The organic layer was dried over Na2SO4, concentrated, and purified by chromatography EA/hexanes) to provide 630 mg (58%) of tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate INT-14. LCMS-ESI (m/z) calculated for C28H32BrN4O3: 538.5; no m/z observed, tR=4.66 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.84-8.78 (s, 2H), 8.31 (t, J=7.0 Hz, 2H), 7.75-7.64 (m, 2H), 7.46-7.38 (m, 2H), 7.30 (dd, J=12.9, 7.1 Hz, 2H), 6.65 (d, J=7.2 Hz, 1H), 5.10-4.94 (m, 1H), 3.43-3.20 (m, 2H), 1.45 (s, 9H), 1.32 (s, 9H).

Workup

  1. customPrepared
  2. concentrationThe reaction mixture was concentrated
  3. dissolutiondissolved in DCM
  4. washwashed with H2O
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by chromatography EA/hexanes)

Sources & evidence

ORD record
ord-7f1b71c5c67448c6a87f8a0f3b96658a
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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