3-(Trifluoromethyl)aniline → HCID 86626629, compound

HRID 556373Notes

Reaction equation

[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C[Al](C)C.C[O:17][C:18]([C:20]1[CH:21]=[N:22][N:23]2[CH:28]=[C:27]([O:29][C:30]3[CH:35]=[C:34]([Cl:36])[N:33]=[C:32]([NH2:37])[N:31]=3)[CH:26]=[CH:25][C:24]=12)=O.CCOC(C)=O.O>C1(C)C=CC=CC=1.C1COCC1>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:4]=[C:5]([NH:6][C:18]([C:20]2[CH:21]=[N:22][N:23]3[CH:28]=[C:27]([O:29][C:30]4[CH:35]=[C:34]([Cl:36])[N:33]=[C:32]([NH2:37])[N:31]=4)[CH:26]=[CH:25][C:24]=23)=[O:17])[CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 5 °C

Procedure

10.5 μl (0.084 mMol) 3-Trifluoromethyl aniline are dissolved in 2 ml toluene and cooled to 5° C. 126 μl Me3Al (2 M solution in toluene; 0.25 mMol) are added slowly via a syringe followed by a solution of 27 mg (0.084 mMol) 6-(2-amino-6-chloro-pyrimidin-4-yloxy)-pyrazolo[1,5-a]pyridine-3-carboxylic acid methyl ester in 1 ml THF. The reaction is stirred at rt for 1 h and then heated to 110° C. for 30 min. The reaction is submitted to aq. workup with EtOAc/H2O. The organic layers are combined, dried and concentrated to give the crude product which is further purified by flash chromatography (SiO2, 4 g column, CH2Cl2/MeOH; gradient 0-10% MeOH) to give the title compound as a white solid: m.p.: 219-221° C.; MS: [M+1]+=449.

Workup

temperatureheated to 110° C. for 30 min
customdried
concentrationconcentrated
customto give the crude product which
customis further purified by flash chromatography (SiO2, 4 g column, CH2Cl2/MeOH; gradient 0-10% MeOH)

Sources & evidence

ORD record: ord-3070c1aa9c844226ac52fdea1860d214
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08058276B2

Reaction notes

Loading…