Dimethylformamide → 1-(8-Fluoro-2-phenyl-quinolin-7-yl)-3-(5-methanesulfonylmethylthiazol-2-ylsulfanyl)-imidazo[1,5-a]pyrazin-8-ylamine

HRID 1992433Notes

Reaction equation

HRID 1992433 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8](=[S:28])[NH:9][C:10]=2[C:11]2[C:20]([F:21])=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.Cl[C:30]1[S:31][C:32]([CH2:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:33][N:34]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>>[F:21][C:20]1[C:11]([C:10]2[N:9]=[C:8]([S:28][C:30]3[S:31][C:32]([CH2:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:33][N:34]=3)[N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=23)=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:16]=[CH:15]2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 14806812-Chloro-5-(methylsulfonylmethyl)-1,3-thiazoleHCID 167536808-Amino-1-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazine-3-thiol

Product 1

HCID 167536771-(8-Fluoro-2-phenyl-quinolin-7-yl)-3-(5-methanesulfonylmethylthiazol-2-ylsulfanyl)-imidazo[1,5-a]pyrazin-8-ylamine

Conditions

Temperature
100 °C

Procedure

A 10 mL microwave vessel was charged with a solution of 8-amino-1-(8-fluoro-2-phenyl-quinolin-7-yl)-2H-imidazo[1,5-a]pyrazine-3-thione (24 mg, 0.000062 mol), 2-chloro-5-[(methylsulfonyl)methyl]-1,3-thiazole (0.026 g, 0.00012 mol), potassium carbonate in DMF (1.7 mL, 0.022 mol). The reaction mixture was heated in the microwave at 100° C. for 10 min. The reaction mixture was heated again at 120° C. for 10 min in the microwave to get full consumption of SM. Reaction mixture was purified by Gilson HPLC eluting with 10→65% acetonitrile: H2O to afford the title compound as an off white solid. 1H NMR (400 MHz, CDCl3): δ=2.85 (s, 3H), 4.36 (s, 2H), 7.34 (d, J=4.80 Hz, 1H), 7.48-7.59 (m, 4H), 7.67 (s, 1H), 7.74-7.78 (m, 2H), 8.04 (d, J=8.84 Hz, 1H), 8.24 (dd, J=8.21, 1.39 Hz, 2H), 8.31 (dd, J=8.72, 1.39 Hz, 1H). MS (ES+): m/z 563.18 (100) [MH+]. HPLC: tR=2.89 min (Open Lynx polar—5 min).

Workup

  1. temperatureThe reaction mixture was heated again at 120° C. for 10 min in the microwave
  2. customto get full
  3. customconsumption of SM
  4. customReaction mixture
  5. customwas purified by Gilson HPLC
  6. washeluting with 10→65% acetonitrile

Sources & evidence

ORD record
ord-5387cdb330b34da5b2d0fdf945ece779
Source dataset
uspto-grants-2010_01
Patent number
US07648987B2

Reaction notes

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