Potassium Phosphate, Tribasic → 6-(4-(Aminomethyl)phenyl)-1-(cyclohexylmethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388106Notes

Reaction equation

HRID 388106 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]4[CH:31]=[CH:30][C:20]([CH2:21][NH:22]C(=O)OC(C)(C)C)=[CH:19][CH:18]=4)[N:15]=3)[NH:10][C:9]2=[O:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.BrC1N=C2N(CC3CCCCC3)C(=O)NC2=NC=1.C(NCC1C=CC(B(O)O)=CC=1)(OC(C)(C)C)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.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]>[NH2:22][CH2:21][C:20]1[CH:19]=[CH:18][C:17]([C:14]2[N:15]=[C:16]3[N:8]([CH2:7][CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)[C:9](=[O:32])[NH:10][C:11]3=[N:12][CH:13]=2)=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 38631634-(tert-Butoxycarbonylaminomethyl)phenylboronic acidHCID 866263916-Bromo-1-(cyclohexylmethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 86626393tert-Butyl 4-(3-(cyclohexylmethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzylcarbamate

Product 1

HCID 573943616-(4-(Aminomethyl)phenyl)-1-(cyclohexylmethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 4-(3-(cyclohexylmethyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzylcarbamate. 6-Bromo-1-(cyclohexylmethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 55.B) (200 mg, 0.64 mmol), [4-(N-boc-aminomethyl)phenyl]boronic acid (195 mg, 0.77 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (53 mg, 0.06 mmol) and potassium phosphate (550 mg, 2.58 mmol) in DMF (15 mL) and water (1 mL) were reacted according to General Procedure B. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated to approximately one third the original volume and treated with potassium carbonate (1.75 M). The desired product was collected by vacuum filtration, washed with water and dried under high vacuum to provide the title compound. The product was used directly in the next step without further purification or characterization. MS (ESI) m/z 438.1 [M+1]+.

Workup

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe desired fractions were concentrated to approximately one third the original volume
  3. additiontreated with potassium carbonate (1.75 M)
  4. filtrationThe desired product was collected by vacuum filtration
  5. washwashed with water
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-456391c80e8f4601800dd37e42a972cf
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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