Diisopropylethylamine → Methyl 4-[(4-thiophen-3-yl-pyrimidin-2-ylamino)-methyl]-benzoate

HRID 416217Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:12]=[CH:11][S:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:13][CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[S:10]1[CH:11]=[CH:12][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=3)[N:7]=2)=[CH:9]1

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of 14 (680 mg, 3.46 mmol) and methyl 4-(aminomethyl)benzoate (686 mg, 4.51 mmol) in dry 1,4-dioxane (10 mL) was added DIPEA (1.50 mL, 8.65 mmol) and the mixture was heated for 48 h at 130° C. in a sealed tube. Solvents were removed under vacuum and the residue was triturated with a mixture of EtOAc/Et2O, to form a solid, which was collected by filtration and dried. This material was purified by flash chromatography on silica gel (EtOAc/CH2Cl2: 30/70) to afford the title compound 15 (540 mg, 1.66 mmol, 48% yield). 1H NMR: (400 MHz, DMSO-d6) δ (ppm): 8.29-8.23 (m, 2H), 7.88 (d, J=8.4 Hz, 2H), 7.84-7.77 (m, 1H), 7.69-7.59 (m, 2H), 7.52-7.43 (m, 2H), 7.03 (d, J=5.2 Hz, 1H), 4.60 (d, J=6.4 Hz, 2H), 3.81 (s, 3H).

Workup

customSolvents were removed under vacuum
customthe residue was triturated with a mixture of EtOAc/Et2O
customto form a solid, which
filtrationwas collected by filtration
customdried
customThis material was purified by flash chromatography on silica gel (EtOAc/CH2Cl2: 30/70)

Sources & evidence

ORD record: ord-5de42867bb1e4e91b88b7035e774ccd8
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088805B2

Reaction notes

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