Dichloromethane → (4'-(5-Aminopyrazin-2-yl)-5'-fluorobiphenyl-2-yl)methanol

HRID 1523859Notes

Reaction equation

HRID 1523859 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:20]=[CH:21][C:22]([NH2:25])=[N:23][CH:24]=2)=[C:15]([F:26])[CH:14]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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]>[NH2:25][C:22]1[N:23]=[CH:24][C:19]([C:16]2[C:15]([F:26])=[CH:14][C:13]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[CH2:2][OH:1])=[CH:18][CH:17]=2)=[N:20][CH:21]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 43742622-(Hydroxymethyl)phenylboronic AcidHCID 903128885-(4-Bromo-2-fluorophenyl)pyrazin-2-amine

Product 1

HCID 90313341(4'-(5-Aminopyrazin-2-yl)-5'-fluorobiphenyl-2-yl)methanolYield 62%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 2-(hydroxymethyl)phenylboronic acid (1 g, 7 mmol), 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (1.76 g, 6.6 mmol), Pd(dppf)Cl2.CH2Cl2 (483 mg, 0.66 mmol) and Na2CO3 (2.1 g, 20 mmol) in DMF (50 mL) was stirred at 110° Celsius overnight under N2. The solution was concentrated to dryness and the residue purified by FCC to give (4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methanol (1.2 g, 62%). 1H NMR (300 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.02 (d, J=1.4, 1H), 7.90 (m, 1H), 7.57 (d, J=7.4, 1H), 7.49-7.26 (m, 5H), 6.69 (s, 2H), 5.20 (t, J=5.3, 1H), 4.44 (d, J=5.3, 2H).

Workup

  1. concentrationThe solution was concentrated to dryness
  2. customthe residue purified by FCC

Sources & evidence

ORD record
ord-d259fbfc0c7148f5874ce334e6534bc2
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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