Acetic Acid → HCID 178508488, compound

HRID 1992436Notes

Reaction equation

[F:1][C:2]1[C:3]([C:18]2[N:19]=[C:20]([S:28]C)[N:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH2:27])[C:22]=23)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:8]=[CH:7]2.CC(O)=O.Br>>[NH2:27][C:23]1[C:22]2[N:21]([C:20]([SH:28])=[N:19][C:18]=2[C:3]2[C:2]([F:1])=[C:11]3[C:6]([CH:7]=[CH:8][C:9]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[N:10]3)=[CH:5][CH:4]=2)[CH:26]=[CH:25][N:24]=1

Participants

Reactant 3

HCID 176Acetic Acid

HCID 260Hydrogen Bromide2×

HCID 16755134HCID 16755134, compound

Product 1

HCID 178508488HCID 178508488, compound

Conditions

Temperature: 118 °C

Procedure

A solution of 1-(8-fluoro-2-phenyl-quinolin-7-yl)-3-methylsulfanyl-imidazo[1,5-a]pyrazin-8-ylamine (24 mg, 0.000060 mol) in AcOH (1 mL, 0.02 mol) was charged with hydrogen bromide (300 uL, 0.006 mol) and refluxed at 118° C. over weekend. An additional 5 eq of HBr were added and the reaction mixture was heated at 118° C. for 4-5 h. The reaction was stopped and cooled in ice. Orange precipitate formed on cooling in ice. The reaction mixture was concentrated in vacuo and washed with hexanes to obtain the title compound as an orange gummy solid. 1H NMR (400 MHz, CD3OD d4): δ=7.56 (dd, J=7.33, 3.28 Hz, 1H), 7.63-7.68 (m, 4H), 7.84-7.90 (m, 1H), 8.15 (d, J=8.84 Hz, 1H), 8.19-8.25 (m, 2H), 8.37 (d, J=8.59 Hz, 1H), 8.87 (d, J=8.84 Hz, 1H). MS (ES+): m/z 388.21 (100). HPLC: tR=2.42 min (Open Lynx polar—5 min). Note: Precipitate formed on cooling in ice. At rt the compound is oily.

Workup

temperaturethe reaction mixture was heated at 118° C. for 4-5 h
temperaturecooled in ice
customOrange precipitate formed
temperatureon cooling in ice
concentrationThe reaction mixture was concentrated in vacuo
washwashed with hexanes

Sources & evidence

ORD record: ord-fa5033c46aec41338b6a9dd763bc6975
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648987B2

Reaction notes

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