Cesium carbonate → 5-{[(1R,2S)-2-amino cyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carbonitrile

HRID 1504878Notes

Reaction equation

OC(C(F)(F)F)=O.[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[CH:17]=[C:18](Br)[C:19]([C:22]#[N:23])=[N:20][CH:21]=1.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][CH3:33])[N:27]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[CH:17]=[C:18]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][CH3:33])[N:27]=2)[C:19]([C:22]#[N:23])=[N:20][CH:21]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-bromopyridine-2-carbonitrile TFA salt (62 mg, 0.15 mmol), 2-amino-6-ethylpyridine (19 mg, 0.15 mmol), Xantphos (13 mg, 0.023 mmol), Pd2(dba)3 (14 mg, 0.015 mmol), and cesium carbonate (197 mg, 0.606 mmol) was evacuated and backfilled with nitrogen (3×). Dioxane (1 mL) was added, and the reaction mixture was heated to 80° C. for 3 hours. The reaction mixture was allowed to cool to room temperature, filtered, and concentrated under reduced pressure to afford 5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carbonitrile. The material was used without further purification in the subsequent transformation. MS ESI calc'd. for C19H25N6 [M+H]+ 337. found 337.

Workup

customwas evacuated
additionDioxane (1 mL) was added
temperatureto cool to room temperature
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-aae830133771406c92e7674f53f89f0e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216173B2

Reaction notes

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