Cyclohexylamine → N2-Cyclohexyl-4'-cyclopropylmethyl-N2'-methyl-[4,5']bipyrimidinyl-2,2'-diamine

HRID 2359737Notes

Reaction equation

[CH:1]1([CH2:4][C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13](S(C)=O)[N:12]=3)=[CH:9][N:8]=[C:7]([NH:20][CH3:21])[N:6]=2)[CH2:3][CH2:2]1.[CH:22]1([NH2:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>CS(C)=O>[CH:22]1([NH:28][C:13]2[N:12]=[C:11]([C:10]3[C:5]([CH2:4][CH:1]4[CH2:3][CH2:2]4)=[N:6][C:7]([NH:20][CH3:21])=[N:8][CH:9]=3)[CH:16]=[CH:15][N:14]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 4′-(cyclopropylmethyl)-N-methyl-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-amine (5-1) (50 mg, 0.165 mmol) in DMSO (1 mL), cyclohexylamine (94 μL, 0.824 mmol) was added, and the reaction was heated in the microwave at 160° C. for 10 minutes. The crude reaction was purified by reverse-phase HPLC [30-100% organic phase with 3% n-propanol modifier over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 10% MeOH/DCM] to obtain the pure desired product as a white solid (39.0 mg, 69.9% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.04-0.20 (m, 2H) 0.37 (d, J=7.58 Hz, 2H) 0.99-1.19 (m, 2H) 1.19-1.36 (m, 4H) 1.59 (d, J=11.62 Hz, 1H) 1.65-1.80 (m, 2H) 1.88 (d, J=8.59 Hz, 2H) 2.72-2.90 (m, 5H) 3.63-3.80 (m, 1H) 6.68 (d, J=5.05 Hz, 1H) 6.96 (d, J=8.08 Hz, 1H) 7.29 (br. s., 1H) 8.24 (d, J=5.05 Hz, 1H) 8.36 (br. s., 1H). HRMS (ES+) for C19H26N6.H+ [MH+]: calcd, 339.2297; found, 339.2312. UV-LC: 100% UV purity at 254/214 nm; tR=6.70 minutes over 7.75 minutes.

Workup

customThe crude reaction
customwas purified by reverse-phase HPLC [30-100% organic phase with 3% n-propanol modifier over 15 minutes]

Sources & evidence

ORD record: ord-597b682112dd4167973b33c470e8a06d
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08685993B2

Reaction notes

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