Dichloromethane methanol → Tert-butyl (3S,4S)-4-(8-bromo-7-fluoro-2-methyl-1H-imidazo[4,5-C]quinolin-1-YL)-3-fluoropiperidine-1-carboxylate

HRID 588471Notes

Reaction equation

HRID 588471 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][C@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C@@H:14]1[F:26])=[CH:9][C:8]([Br:27])=[C:7]([F:28])[CH:6]=2.CO.C(Cl)Cl.[CH2:34](C(CC)(CC)C([O-])([O-])[O-])[CH3:35]>>[Br:27][C:8]1[C:7]([F:28])=[CH:6][C:5]2[N:4]=[CH:3][C:2]3[N:1]=[C:34]([CH3:35])[N:12]([C@H:13]4[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][C@@H:14]4[F:26])[C:11]=3[C:10]=2[CH:9]=1

Participants

4

Reactant 3

HCID 21226129Dichloromethane methanolHCID 21875354TriethylorthoaceateHCID 117876729Tert-butyl (3S,4S)-4-((3-amino-6-bromo-7-fluoroquinolin-4-YL)amino)-3-fluoropiperidine-1-carboxylate

Product 1

HCID 117876213Tert-butyl (3S,4S)-4-(8-bromo-7-fluoro-2-methyl-1H-imidazo[4,5-C]quinolin-1-YL)-3-fluoropiperidine-1-carboxylate

Procedure

(3S,4S)-tert-butyl 4-((3-amino-6-bromo-7-fluoroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate (27 g, 0.059 mol) was heated in triethylorthoacetate (150 mL) under N2 atmosphere for 5 h at 120° C. The reaction was monitored by TLC (5% MeOH/DCM). The volatiles were concentrated under vacuum, the obtained crude product was purified by column chromatography on silica gel (0-3% MeOH/DCM) to afford (3S,4S)-tert-butyl 4-(8-bromo-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidine-1-carboxylate (15 g, yield from two steps). 1HNMR (CDCl3, 400 MHz): δ 9.28-9.23 (d, 1H), 8.43-8.34 (dd, 1H), 8.01-7.99 (d, 1H), 5.60-5.35 (m, 1H), 5.25-4.85 (m, 1H), 4.75-4.35 (m, 2H), 3.15-2.95 (m, 2H), 2.79 (s, 3H), 2.40-2.05 (m, 2H), 1.57 (s, 9H); LCMS: 100%, m/z=480.8 (M+); HPLC: 97.31%.

Workup

  1. concentrationThe volatiles were concentrated under vacuum
  2. customthe obtained crude product
  3. customwas purified by column chromatography on silica gel (0-3% MeOH/DCM)

Sources & evidence

ORD record
ord-449dde5382eb471c9b2cfb6994a7c6bc
Source dataset
uspto-grants-2016_01
Patent number
US09227969B2

Reaction notes

Loading…