3-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine → HCID 178521577, compound

HRID 1623381Notes

Reaction equation

[Cl:1][C:2]1[C:3]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:4][C:5]([C:8]2[C:13]([Cl:14])=[CH:12][N:11]=[C:10](F)[CH:9]=2)=[CH:6][N:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([OH:31])[CH2:27][CH2:26]1>CS(C)=O>[Cl:14][C:13]1[C:8]([C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[C:3]([NH:16][CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:4]=2)=[CH:9][C:10]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([OH:31])[CH2:27][CH2:26]2)=[N:11][CH:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a scintillation vial containing 3-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (20 mg, 0.056 mmol) was added DMSO (1 ml) and trans-4-aminocyclohexanol (32.2 mg, 0.280 mmol). The reaction mixture was capped and heated to 120° C. in an oil bath for 3 hr. The reaction product was purified by reverse phase preparative HPLC to yield trans-4-(5-chloro-4-(5-chloro-6-((tetrahydro-2H-pyran-4-yl)methyl)aminopyrazin-2-yl)pyridin-2-yl-amino)cyclohexanol (2.2 mg, 4.86 μmol, 8.69% yield), LCMS (m/z): 452.1 (MH+), retention time=0.76 min as a TFA salt after lypholyzing. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.17-1.26 (m, 4H) 1.27-1.39 (m, 2H) 1.58 (dd, J=13.11, 1.76 Hz, 2H) 1.84-2.02 (m, 5H) 3.30 (d, J=7.04 Hz, 4H) 3.43-3.61 (m, 2H) 3.84 (dd, J=11.35, 3.13 Hz, 2H) 6.58 (s, 1H) 7.66 (s, 1H) 7.90 (s, 1H).

Workup

customThe reaction mixture was capped
customThe reaction product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record: ord-57a2a817c41b4f70a6b0c3d1a623f932
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778951B2

Reaction notes

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