p-Toluidine → tert-butyl (3R,4R)-4-(5-cyano-6-(p-tolylamino)pyrazin-2-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

HRID 2200496Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:5]=[N:4][C:3]=1[C:23]#[N:24].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1.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.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:23]([C:3]1[N:4]=[CH:5][C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:2]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)#[N:24]

Participants

Conditions

Temperature: 95 °C

Procedure

To a mixture of tert-butyl (3R,4R)-4-(6-chloro-5-cyanopyrazin-2-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (100 mg, 0.28 mmol) in Dioxane (2 mL) was added p-toluidine (37 mg, 0.35 mmol), Pd(OAc)2 (13 mg, 0.056 mmol), BINAP (35 mg, 0.056 mmol) and K2CO3 (116 mg, 0.84 mmol). After heating at 95° C. for 4 h, the mixture was filtered, the filtrate was concentrated and purified by preparative HPLC to give tert-butyl (3R,4R)-4-(5-cyano-6-(p-tolylamino)pyrazin-2-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (53 mg).

Workup

filtrationthe mixture was filtered
concentrationthe filtrate was concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-2189705d7bfb4d7fa2cf523a9b24bebf
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359308B2

Reaction notes

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