5-Bromo-2-iodopyrimidine → HCID 86689679, compound

HRID 1775832Notes

Reaction equation

HRID 1775832 reaction equation
[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][C@@H:13]([CH2:21][C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:37][C:38]1[CH:39]=[N:40][C:41](I)=[N:42][CH:43]=1.C(#N)C.C1COCC1>O.CC(=O)OCC.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:37][C:38]1[CH:39]=[N:40][C:41]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][C@H:13]([NH:12][C:10]([C:8]3[S:9][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:6][CH:7]=3)=[O:11])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:27][CH:26]=2)=[N:42][CH:43]=1

Participants

7

Reactant 3

HCID 70066515-Bromo-2-iodopyrimidineHCID 22177404Acetonitrile tetrahydrofuranHCID 86689680HCID 86689680, compound

Product 1

HCID 86689679HCID 86689679, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Prepared using General Procedure 10. Into a degassed solution of tert-butyl (S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate INT-16 (510 mg, 1.0 mmol) and 5-bromo-2-iodopyrimidine (570 mg, 2.0 mmol) in 2/2/1 ACN/THF/saturated aqueous NaHCO3 (10 mL) was added Pd(dppf)Cl2 (30 mg, 0.4 mmol). The reaction mixture was heated at 120° C. for 1 h in a microwave reactor. The reaction mixture was diluted with water (100 mL) and EA (50 mL) and filtered over Celite. The aqueous layer was extracted with EA (3×30 mL) and the combined organic layer was dried over MgSO4, concentrated, and purified by chromatography (EA/hexanes) to provide 342 mg (63%) of tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanoate INT-17. LCMS-ESI (m/z) calculated for C26H30BrN3O3: 543.1. found: 488.0 [M−tBu+H]+, tR=10.95 min (Method 2).

Workup

  1. customPrepared
  2. filtrationfiltered over Celite
  3. extractionThe aqueous layer was extracted with EA (3×30 mL)
  4. dry with materialthe combined organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. custompurified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-bf5ea517323c449788b2404c408772a1
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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