Sodium Carbonate → HCID 178516213, compound

HRID 388119Notes

Reaction equation

HRID 388119 reaction equation
BrC1N=C2N(CCN3CCCC3=O)C(=O)NC2=NC=1.[NH:20]1[CH:24]=[N:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[N:36]=[C:35]4[N:37]([CH2:41][CH2:42][N:43]5[CH2:47][CH2:46][CH2:45][C:44]5=[O:48])[C:38](=[O:40])[NH:39][C:34]4=[N:33][CH:32]=3)=[CH:27][CH:26]=2)=[N:21]1.Cl.N1C(C2C=CC(B(O)O)=CC=2)=NC=N1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O1CCOCC1>[NH:20]1[CH:24]=[N:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[N:36]=[C:35]4[N:37]([CH2:41][CH2:42][N:43]5[CH2:47][CH2:46][CH2:45][C:44]5=[O:48])[C:38](=[O:40])[NH:39][C:34]4=[N:33][CH:32]=3)=[CH:27][CH:26]=2)=[N:21]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66699876HCID 66699876, compoundHCID 178516214HCID 178516214, compound

Product 1

HCID 178516213HCID 178516213, compoundYield 7.4%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 312751,4-DioxaneSolvent

Procedure

6-(4-(1H-1,2,4-Triazol-3-yl)phenyl)-1-(2-(2-oxopyrrolidin-1-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one 6-Bromo-1-(2-(2-oxopyrrolidin-1-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 157.A) (290 mg, 0.8 mmol), 4-(1H-1,2,4-triazol-5-yl)phenylboronic acid hydrochloride (See Example 159.D) (224 mg, 0.99 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (30 mg, 0.04 mmol), 1M sodium carbonate (2.5 mL, 2.5 mmol), and dioxane (5 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 1 h. The reaction was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were passed through a Strata-XC ion-exchange column and the product was released from the column with 2M ammonia in methanol. The solution was concentrated and the resulting material was triturated with either to give a white solid (23 mg, 7% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.48 (br, 1H), 8.20 (d, J=10.0, 2H), 8.13 (d, J=10.0, 2H), 4.06 (m, 2H), 3.58 (m, 2H), 3.52 (t, J=6.8, 2H), 1.85 (d, J=7.8, 2H), 1.74 (m, 2H); MS (ESI) m/z 391.5 [M+1]+; mp 300-301° C.

Workup

  1. customThe reaction was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe solution was concentrated
  3. customthe resulting material was triturated with either

Sources & evidence

ORD record
ord-871120a9aac14674be2de4ab7c0511f8
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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