Diisopropylethylamine → Epz015666

HRID 880332Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:9])[CH:3]=1.[O:25]1[CH2:28][CH:27]([NH2:29])[CH2:26]1.CCN(C(C)C)C(C)C>CC(O)C>[CH2:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:22][CH2:23][N:14]1[CH2:13][C@@H:12]([OH:24])[CH2:11][NH:10][C:8]([C:4]1[CH:3]=[C:2]([NH:29][CH:27]2[CH2:28][O:25][CH2:26]2)[N:7]=[CH:6][N:5]=1)=[O:9]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxy propyl)pyrimidine-4-carboxamide (347 mg, 1 mmol) in i-PrOH (5 mL) was added oxetan-3-amine (73.1 mg, 1 mmol) and DIPEA (129 mg, 1 mmol). The resulting mixture was stirred at 110° C. for 16 hours, at which time LCMS showed the completion of the reaction. After evaporation of the solvent, the residue was purified by preparative HPLC to give the target compound (S)—N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide (62.5 mg, yield: 16.3%). 1H NMR (400 MHz, MeOD-d4) δ 8.24 (s, 1H), 7.15-7.05 (m, 4H), 7.02-6.98 (m, 1H), 5.09 (s, 1H), 4.95 (t, J=6.8 Hz, 2H), 4.59 (t, J=6.3 Hz, 2H), 4.10-4.03 (m, 1H), 3.72 (s, 2H), 3.56-3.46 (m, 2H), 2.96-2.91 (m, 2H), 2.87-2.80 (m, 2H), 2.65 (d, J=6.3 Hz, 2H). LCMS (m/z): 384.1 [M+H]+.

Workup

customthe completion of the reaction
customAfter evaporation of the solvent
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-9ec85e2285f94b5496715f9aee7fd1fe
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993555B2

Reaction notes

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