2-Bromopyrimidine → 4-(1-Pyrimidin-2-ylpiperidin-4-ylamino)benzoic acid tert-butyl ester

HRID 1274155Notes

Reaction equation

Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([O:12][C:13](=[O:27])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:16][CH:15]=1)([CH3:11])([CH3:10])[CH3:9]>C(O)(C)(C)C>[C:8]([O:12][C:13](=[O:27])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]2[CH2:26][CH2:25][N:24]([C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:23][CH2:22]2)=[CH:16][CH:15]=1)([CH3:11])([CH3:9])[CH3:10]

Participants

Conditions

Temperature: 90 °C

Procedure

2-Bromopyrimidine (0.016 g, 0.1 mmol) was added to a solution of (49) (0.032 g, 0.12 mmol) in tert-butyl alcohol (2 mL) at 25° C. The mixture was heated to 90° C. and was maintained at that temperature for 12 h. The reaction mixture was then cooled to room temperature and concentrated to a yellow oily residue. Purification of the residue by flash column chromatography (gradient elution 0 to 20% EtOAc in hexanes) provided the title compound (0.032 g, 89%): TLC (Rf =0.41; 40% EtOAc/hexanes); 1H NMR (CDCl3) δ 8.29 (d, 2H, J=4.7), 7.80 (d, 2H, J=8.8), 6.54 (d, 2H, J=8.8), 6.46 (t, 1H, J=4.7), 4.66 (d, 2H, J=13.7), 3.96 (d, 1H, J=7.8), 3.63 (m, 1H), 3.13 (t, 2H, J=12.0), 2.12 (d, 2H, J=12.0), 1.54 (s, 9H), 1.43 (m, 2H); 13C NMR (CDCl3) δ 166.1, 161.6, 157.8, 150.3, 131.5, 120.5, 111.8, 109.8, 79.9, 50.1, 42.6, 32.1, 28.3; HRMS (FAB) m/z 355.2126 (M+H)+ (C20H26N4O2 requires 355.2134).

Workup

temperaturewas maintained at that temperature for 12 h
temperatureThe reaction mixture was then cooled to room temperature
concentrationconcentrated to a yellow oily residue
customPurification of the residue
washby flash column chromatography (gradient elution 0 to 20% EtOAc in hexanes)

Sources & evidence

ORD record: ord-03e17524235a492c81ce319dd9f52b54
Source dataset: uspto-grants-2000_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06156758

Reaction notes

Loading…