Cesium carbonate → 2-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl]amino)-N-methylbenzamide

HRID 62519

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([NH2:27])[CH:23]=[N:22]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.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[CH:7][C:2]([NH:27][C:24]2[CH:23]=[N:22][N:21]([CH3:20])[C:25]=2[CH3:26])=[N:3][CH:4]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a 10 mL sealable tube was added 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methylbenzamide (95 mg, 0.321 mmol), 1,5-dimethyl-1H-pyrazol-4-amine (35.7 mg, 0.321 mmol), BINAP (20 mg, 0.032 mmol), cesium carbonate (314 mg, 0.964 mmol), and palladium(II) acetate (7.21 mg, 0.032 mmol) in 1,4-dioxane (5 mL). The reaction vessel was sealed and heated at 150° C. for 1 hr. The reaction mixture was purified using a prep HPLC (0.1% formic acid, 5 to 95% water:acetonitrile). Fractions were combined and evaporated. 2-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-methylbenzamide (16 mg, 0.037 mmol, 11.38% yield) was isolated as yellow oil LCMS (M+H)+=371.1; 1H NMR (400 MHz, MeOD) ppm 2.17 (s, 3 H) 2.91 (s, 3 H) 3.78 (s, 3 H) 6.47 (s, 1 H) 7.13-7.24 (m, 1 H) 7.40 (s, 1 H) 7.46-7.57 (m, 2 H) 7.67 (dd, J=7.83, 1.26 Hz, 1 H) 7.82 (s, 1 H).

Workup

customThe reaction vessel was sealed
customThe reaction mixture was purified
customevaporated

Sources & evidence

ORD record: ord-4ce76db3c0cd41a6ac45f12fabf326b1
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09446034B2

Linked notes

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