Benzonitrile, 4-bromo- → 4'-(2,4-Diamino-pyrimidin-5-ylmethyl)-2',6'-diethoxy-biphenyl-4-carbonitrile

HRID 2416305Notes

Reaction equation

HRID 2416305 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[CH2:33]([O:35][C:36]1[CH:37]=[C:38]([CH:48]=[C:49]([O:52][CH2:53][CH3:54])[C:50]=1I)[CH2:39][C:40]1[C:41]([NH2:47])=[N:42][C:43]([NH2:46])=[N:44][CH:45]=1)[CH3:34].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[NH2:46][C:43]1[N:42]=[C:41]([NH2:47])[C:40]([CH2:39][C:38]2[CH:37]=[C:36]([O:35][CH2:33][CH3:34])[C:50]([C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=3)=[C:49]([O:52][CH2:53][CH3:54])[CH:48]=2)=[CH:45][N:44]=1

Participants

8

Reactant 5

HCID 12162Benzonitrile, 4-bromo-HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 226369195-(3,5-Diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine

Product 1

HCID 226369554'-(2,4-Diamino-pyrimidin-5-ylmethyl)-2',6'-diethoxy-biphenyl-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

4-Bromo-benzonitrile (186 mg; 1 mmol), bis(pinacolato)diboron (279 mg; 1.1 mmol), potassium acetate (294 mg; 3 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium(II) (PdCl2(dppf)) (46 mg; 0.06 mmol) are stirred in dimethylformamide (6 ml; dried over a molecular sieve) at a bath temperature of 80° C. for 3 hours while gassing with argon. After cooling to room temperature, dimethylformamide (20 ml; dried over a molecular sieve), tetrakis-triphenylphosphine-palladium (90 mg; 0.078 mmol), 5-(3,5-diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (example 1) (331 mg; 0.8 mmol) and a 2 M aqueous potassium phosphate solution (4 ml) are added. The reaction mixture is stirred for approx. 1.5 hours at 80° C., cooled to room temperature and concentrated. The residue obtained is chromatographed over silica gel (100 g) with methylene chloride/methanol/NH4OH (19/1/0.05)0.61 mg (20%) 4′-(2,4-diamino-pyrimidin-5-ylmethyl)-2′,6′-diethoxy-biphenyl-4-carbonitrile are obtained as a beige powder.

Workup

  1. customdried over a molecular sieve) at a bath temperature of 80° C. for 3 hours
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. customThe residue obtained
  5. customis chromatographed over silica gel (100 g) with methylene chloride/methanol/NH4OH (19/1/0.05)0.61 mg (20%) 4′-(2,4-diamino-pyrimidin-5-ylmethyl)-2′,6′-diethoxy-biphenyl-4-carbonitrile
  6. customare obtained as a beige powder

Sources & evidence

ORD record
ord-7c48c299126c45f3904a3b83eea57cfd
Source dataset
uspto-grants-2004_11
Patent number
US06821980B1

Reaction notes

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