Hydrochloric Acid → HCID 178482965, compound

HRID 1963961Notes

Reaction equation

[Cl:1][C:2]1[C:3]([C:9]2[N:14]=[C:13]([N:15]([CH3:23])[CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:12]=[N:11][CH:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.C(OC(=O)[NH:30][CH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([NH2:38])[CH2:34][CH2:33]1)(C)(C)C.Cl>CS(C)=O>[NH2:30][CH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([NH:38][C:5]2[CH:4]=[C:3]([C:9]3[N:14]=[C:13]([N:15]([CH3:23])[CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH:12]=[N:11][CH:10]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:34][CH2:33]1

Participants

Conditions

Temperature: 102.5 °C

Procedure

A mixture of 6-(5-chloro-2-fluoropyridin-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (15 mg, 0.045 mmol), DMSO (0.4 ml), and tert-butyl(trans-4-aminocyclohexyl)methylcarbamate (92 mg, 0.401 mmol) was stirred at 100-105° C. for 18 hours, and the reaction progress was followed by LCMS. To the crude intermediate was added 6 M aq.HCl (120 μl, 0.720 mmol) and heated at 80° C. for 40 minutes, and the reaction progress was followed by LCMS. The reaction mixture was let cool, added 0.5 ml of DMSO, filtered and purified by prep LC. After lyophilization, 15.6 mg of the title compound, as a TFA salt was obtained. LCMS (m/z): 445.2 (MH+), retention time=0.59 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.12-1.47 (m, 6H) 1.59 (d, J=12.60 Hz, 2H) 1.67 (ddd, J=7.18, 3.81, 3.66 Hz, 1H) 1.92 (d, J=12.31 Hz, 2 H) 2.01-2.11 (m, 1 H) 2.16 (d, J=11.43 Hz, 2 H) 2.83 (d, J=7.03 Hz, 2 H) 3.17 (s, 3H) 3.33-3.45 (m, 2 H) 3.56 (d, J=7.33 Hz, 2 H) 3.60-3.72 (m, 1 H) 3.93 (dd, J=11.14, 2.93 Hz, 2 H) 6.92 (s, 1 H) 8.02 (d, J=2.64 Hz, 2 H) 8.11 (s, 1 H).

Workup

temperatureThe reaction mixture was let cool
filtrationfiltered
custompurified by prep LC

Sources & evidence

ORD record: ord-30f7e4e1d44c4724bedb42d6b9a13452
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415381B2

Reaction notes

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