Ammonia → 3-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

HRID 1191091Notes

Reaction equation

[CH:1]1([CH2:4][NH:5][C:6]2[S:7][CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=3)[N:10]=2)[CH2:3][CH2:2]1.N.[H][H]>[Ni].CO>[NH2:16][CH2:15][C:14]1[CH:13]=[N:12][C:11]([C:9]2[N:10]=[C:6]([NH:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[S:7][CH:8]=2)=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Add 6-[2-(cyclopropylmethylamino)-thiazol-4-yl]-nicotinonitrile (2.0 g, 7.8 mmol), Raney Nickel (2.0 mL), and 2M ammonia in methanol (200 mL) to a pressure vessel under a nitrogen atmosphere. Pressurize the vessel to 60 psi with hydrogen, and stir the mixture for 6 h at 40° C. Filter the mixture through Celite® and concentrate in vacuo to an oil. Dissolve the oil in EtOAc (300 mL) and saturated ammonium hydroxide (50 mL). Stir the solution for 20 h in a sealed flask at room temperature. Collect the organic layer and concentrate in vacuo. Purify the crude mixture by SCX chromatography followed by chromatography on silica gel (150 g) eluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient) to obtain the title compound (1.05 g, 51%). MS (ES+) m/z: 261 (M+H)+.

Workup

filtrationFilter the mixture through Celite®
concentrationconcentrate in vacuo to an oil
dissolutionDissolve the oil in EtOAc (300 mL)
stirringStir the solution for 20 h in a sealed flask at room temperature
customCollect the organic layer
concentrationconcentrate in vacuo
customPurify the crude mixture by SCX chromatography
washeluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient)

Sources & evidence

ORD record: ord-419a6b6d4fbd471097ca9e1e8522e50f
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680091B2

Reaction notes

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