Diisopropylethylamine → (4-phenethyloxy-cyclohexyl)-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-amine

HRID 271329Notes

Reaction equation

[C:1]1([CH2:7][CH2:8][O:9][C@H:10]2[CH2:15][CH2:14][C@H:13]([NH2:16])[CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:18]1[N:23]=[CH:22][N:21]=[C:20]2[NH:24][N:25]=[CH:26][C:19]=12.C(N(CC)C(C)C)(C)C>CC(O)C>[CH2:8]([O:9][CH:10]1[CH2:15][CH2:14][CH:13]([NH:16][C:18]2[N:23]=[CH:22][N:21]=[C:20]3[NH:24][N:25]=[CH:26][C:19]=23)[CH2:12][CH2:11]1)[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 219 mg of trans-4-(2-phenyl-ethoxy)-cyclohexylamine, 154 mg of 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (R. K. Robins, J. Amer. Chem. Soc., 78, 784-790 (1956)), 10 mL of 2-propanol and 0.174 mL of N,N-diisopropyl-ethylamine was heated to 80° C. for 12 hours. The mixture was cooled and concentrated under reduced pressure and purified by either preparative TLC eluting with 50:50:5 THF:diethyl ether:NH4OH or preparative reverse phase chromatography on delta Pak C (C-18 column) eluting with a gradient of 90:10 to 0:100 of 0.1% TFA in H2O: CH3CN gave 60-92% of (4-phenethyloxy-cyclohexyl)-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-amine as a white crystalline solid. MS (m+1)=338.32; 1H NMR (400 MHz, CDCl3) 8.43 (s, 1H), 7.92 (s, 1H), 7.3-7.2 (m, 5H), 3.7 (t, 2H), 3.3 (m, 1H), 2.9 (t, 2H), 2.22 (d, 2H), 2.1 (d, 2H), 1.7 (m, 1H), 1.5 (dd, 2H), 1.4 (m, 2H).

Workup

temperatureThe mixture was cooled
concentrationconcentrated under reduced pressure
custompurified by either preparative TLC
washeluting with 50:50:5 THF
washdiethyl ether:NH4OH or preparative reverse phase chromatography on delta Pak C (C-18 column) eluting with a gradient of 90:10 to 0:100 of 0.1% TFA in H2O

Sources & evidence

ORD record: ord-e9e6e7e07b04446583ace8012adf3970
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07452893B2

Reaction notes

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