P-Anisidine → HCID 56969137, compound

HRID 513261Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

(S)-4-(1-acetylpiperidin-3-ylamino)-6-chloronicotinamide (50 mg, 0.17 mmol), p-anisidine (31 mg, 0.26 mmol), Cs2CO3 (111 mg, 0.34 mmol), BINAP (16 mg, 0.026 mmol), and Pd(OAc)2 (4 mg, 0.017 mmol) and degassed dioxane (4 mL) were heated to 100° C. under Argon overnight. The following morning the mixture was determined to be complete by UPLC. The reaction was diluted with water, acetonitrile, and TFA, then purified by HPLC affording 4 mg of the desired product after lyophilization. MS found for C20H25N5O3 as (M+H)+ 384.3. UV: λ=202, 257 nm. 1H NMR: (CD3OD) (mixture of rotamers) δ 8.12 (s, 0.4H), 8.06 (s, 0.6H), 7.24 (dd, 2H), 7.06 (dd, 2H), 5.98 (s, 0.7H), 5.89 (s, 0.3H), 3.84 (s, 3H), 3.40-3.68 (m, 5H), 2.13 (s, 2H), 2.03 (m, 1H), 1.98 (s, 1H), 1.52-1.93 (m, 3H).

Workup

custompurified by HPLC

Sources & evidence

ORD record: ord-8af4b67ca17347edadbd69641123836b
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102625B2

Reaction notes

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