Dichloromethane → HCID 54761628, compound

HRID 589878Notes

Reaction equation

HRID 589878 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[C:14]([NH:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]2[C:27]([CH:34]3[CH2:36][CH2:35]3)=[C:28](Br)[C:29]([C:30]([NH2:32])=[O:31])=[C:23]2[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O.O1CCCC1.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]>[C:14]([NH:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]2[C:27]([CH:34]3[CH2:35][CH2:36]3)=[C:28]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=3)[C:29]([C:30]([NH2:32])=[O:31])=[C:23]2[CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 66584858HCID 66584858, compound

Product 1

HCID 54761628HCID 54761628, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a mixture of 57.0 mg (0.300 mmol) of (3-trifluoromethylphenyl)boronic acid and 76.7 mg (0.200 mmol) of N2-tert-butyl-7-bromo-6-cyclopropyl-3,4-dihydropyrrolo-[1,2-a]pyrazine-2,8(1H)-dicarboxamide in a reaction tube are added 2 ml of tetrahydrofuran degassed beforehand under argon for 15 minutes and 63.6 mg (0.60 mmol) of disodium carbonate dissolved in 1 ml of water. The tube is then purged with argon, and about 16 mg (0.02 mmol) of a complex of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) and dichloromethane (PdCl2(dppf).CH2Cl2—CAS 95464-05-4) suspended in 2 ml of tetrahydrofuran degassed beforehand under argon are added. The tube is then stirred at 70° C. for 20 hours, the mixture is cooled and the solvent is evaporated off under reduced pressure. The residue is taken up in 5 ml of tetrahydrofuran and 100 mg of propanethiol-grafted silica (Si-Thiol, Biotage) are added. The mixture is stirred for 4 hours at room temperature and the grafted silica is separated out by filtration on a Celite cartridge, the Celite is washed twice with 1 ml of tetrahydrofuran and the filtrate is concentrated under reduced pressure. The residue is then purified by SFC purification, to give 0.017 g of N2-tert-butyl-6-cyclopropyl-7-(3-trifluoromethyl-phenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide.

Workup

  1. customdegassed beforehand under argon for 15 minutes
  2. customdegassed beforehand under argon
  3. additionare added
  4. temperaturethe mixture is cooled
  5. customthe solvent is evaporated off under reduced pressure
  6. addition100 mg of propanethiol-grafted silica (Si-Thiol, Biotage) are added
  7. stirringThe mixture is stirred for 4 hours at room temperature
  8. customthe grafted silica is separated out by filtration on a Celite cartridge
  9. washthe Celite is washed twice with 1 ml of tetrahydrofuran
  10. concentrationthe filtrate is concentrated under reduced pressure
  11. customThe residue is then purified by SFC purification

Sources & evidence

ORD record
ord-08e8ed34db26473496d92d11e8795e67
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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