Triethylamine → 4-(4-Aminonaphthalen-1-yloxy)pyrimidin-2-amine

HRID 2069153Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([NH:19]C(=O)OC(C)(C)C)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C([N:29](CC)CC)C.COC1C=CC(CN)=CC=1>CS(C)=O>[NH2:19][C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:29])[N:7]=2)=[CH:10][CH:11]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of tert-butyl 4-(2-chloropyrimidin-4-yloxy)naphthalen-1-ylcarbamate (1.00 g, 2.69 mmol) and triethylamine (0.374 mL, 2.69 mmol) in DMSO (10 mL) was added (4-methoxyphenyl)methanamine (350 μl, 2.69 mmol) and the reaction mixture was heated in a sealed tube at 95° C. for 16 hr. The resulting mixture was partitioned between water and EtOAc and the organic layer was separated and washed with brine and then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, ethyl acetate in isohexane, 0-50%, gradient elution) to afford [as judged by LCMS] a 1:1 mixture of the desired compound: tert-butyl 4-(2-(4-methoxybenzylamino)pyrimidin-4-yloxy)naphthalen-1-ylcarbamate together with 2-chloro-N-(4-methoxybenzyl)pyrimidin-4-amine. This material was used directly in the next step without further purification.

Workup

customThe resulting mixture was partitioned between water and EtOAc
customthe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
customevaporated in vacuo
customThe residue was purified by flash column chromatography (SiO2, ethyl acetate in isohexane, 0-50%, gradient elution)
customto afford [as judged by LCMS]

Sources & evidence

ORD record: ord-27036b22ab4940fe8f0e46af07395db2
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299074B2

Reaction notes

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