m-Toluidine → HCID 69284811, compound

HRID 2201144Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:12]2([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)[CH2:10][CH3:11])[C:5]([F:26])=[CH:4][C:3]=1[C:27]#[N:28].[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=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.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:27]([C:3]1[CH:4]=[C:5]([F:26])[C:6]([NH:8][C@H:9]([C:12]2([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)[CH2:10][CH3:11])=[N:7][C:2]=1[NH:29][C:30]1[CH:31]=[C:32]([CH3:36])[CH:33]=[CH:34][CH:35]=1)#[N:28]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (S)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamate (60 mg, 0.15 mmol) in dioxane (1 mL) was added m-toluidine (19 mg, 0.18 mmol), BINAP (18.7 mg, 0.03 mmol), Pd(OAc)2 (6.7 mg, 0.03 mmol) and Cs2CO3 (146 mg, 0.45 mmol). After degassed with Argon, the mixture was heated at 80° C. for 15 h. The mixture was diluted with dioxane, precipitate was filtered off, filter cake was washed with ACN, the filtrate was concentrated and purified by column to give of (S)-benzyl 1-(1-(5-cyano-3-fluoro-6-(m-tolylamino)pyridin-2-ylamino)propyl)cyclopropylcarbamate (55 mg).

Workup

customAfter degassed with Argon
additionThe mixture was diluted with dioxane, precipitate
filtrationwas filtered off
filtrationfilter cake
washwas washed with ACN
concentrationthe filtrate was concentrated
custompurified by column

Sources & evidence

ORD record: ord-48785cd2657a450aa826b5a8e2d5c41b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359375B2

Reaction notes

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