Methylamine → HCID 178482386, compound

HRID 707421Notes

Reaction equation

[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@@H:13]([NH:15][C:16]2[C:21](Cl)=[N:20][CH:19]=[CH:18][N:17]=2)[CH2:12]1.CC(C)([O-])C.[Na+].[CH3:29][NH2:30].C1COCC1>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:21]([NH:30][CH3:29])=[N:20][CH:19]=[CH:18][N:17]=2)[CH2:12]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a glass microwave reaction vessel was added cis-N1-(benzo[d]thiazol-2-yl)-N3-(3-chloropyrazin-2-yl)cyclobutane-1,3-diamine (Intermediate 81, 0.1952 g, 0.588 mmol), sodium tert-butoxide (0.226 g, 2.353 mmol, Sigma-Aldrich Chemical Company, Inc.), and BrettPhos precatalyst (7.05 mg, 8.82 mol, Strem Chemicals, Inc.), and methanamine solution, 2.0 M in THF (1.471 ml, 2.94 mmol, Sigma-Aldrich Chemical Company, Inc.) in dioxane (1.177 ml) to stir at 50° C. for 3 h. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (25 g), eluting with a gradient of 1% to 8% MeOH in CH2Cl2, to provide the title compound (110 mg, 0.337 mmol, 57.3% yield). LCMS showed product peak at 1.26 min (m+1=327.0). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.82-1.95 (m, 2 H) 2.80-2.91 (m, 5 H) 4.00-4.18 (m, 2 H) 6.31 (br. s., 1 H) 6.38 (d, J=6.06 Hz, 1 H) 7.03 (td, J=7.63, 1.17 Hz, 1 H) 7.20 (d, J=3.13 Hz, 1 H) 7.21-7.28 (m, 2 H) 7.41 (d, J=7.43 Hz, 1 H) 7.69 (dd, J=7.82, 0.78 Hz, 1 H) 8.36 (d, J=6.85 Hz, 1 H)

Workup

customTo a glass microwave reaction vessel
customchromatographed through a Biotage SNAP HP-silica gel column (25 g)
washeluting with a gradient of 1% to 8% MeOH in CH2Cl2

Sources & evidence

ORD record: ord-ec20421b96004d2aadcdceabd8863b44
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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