Cesium carbonate → HCID 131734944, compound

HRID 921880Notes

Reaction equation

Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[CH3:19][N:20]1[CH2:25][CH2:24][N:23]2[CH2:26][CH2:27][NH:28][CH2:29][CH:22]2[C:21]1=[O:30].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:3]1[C:2]([N:28]2[CH2:27][CH2:26][N:23]3[CH2:24][CH2:25][N:20]([CH3:19])[C:21](=[O:30])[CH:22]3[CH2:29]2)=[CH:7][C:6]([C:8]#[N:9])=[CH:5][C:4]=1[NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of crude (+/−)-tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (78 mg, 0.236 mmol), 2-methyloctahydro-1H-pyrazino[1,2-a]pyrazin-1-one (40 mg, 0.236 mmol), Pd2dba3 (21.65 mg, 0.024 mmol), BINAP (44.2 mg, 0.071 mmol) and Cs2CO3 (231 mg, 0.709 mmol) in Dioxane (2.5 mL) was evacuated and filled with nitrogen 3 times and heated at 105° C. for 8 h. LC-MS showed completion of reaction. The reaction mixture was filtered through a plug of Celite and the filtrate was concentrated. Purification via flash chromatography (0-5% MeOH in DCM, 12 g) gave (+/−)-tert-butyl (2-chloro-5-cyano-3-(8-methyl-9-oxohexahydro-1H-pyrazino[1,2-a]pyrazin-2(6H)-yl)phenyl)carbamate (60 mg) as a yellow oil.

Workup

customwas evacuated
additionfilled with nitrogen 3 times
customcompletion of reaction
filtrationThe reaction mixture was filtered through a plug of Celite
concentrationthe filtrate was concentrated
customPurification via flash chromatography (0-5% MeOH in DCM, 12 g)

Sources & evidence

ORD record: ord-aa86f92ae92c40938d8b044c7be3a325
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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