Trifluoroacetic acid → HCID 178434459, compound

HRID 2241213Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15](CC3C=CC(OC)=CC=3)[N:16]=[C:17]([CH3:18])[C:10]=12.FC(F)(F)C(O)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[NH:15][N:16]=[C:17]([CH3:18])[C:10]=12

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 68517223HCID 68517223, compound

Product 1

HCID 178434459HCID 178434459, compoundYield 86.7%

Conditions

Temperature: 80 °C

Procedure

A 100 mL round-bottomed flask was charged with 1-(4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(pyridin-2-yl)urea (21.3 mg, 0.0427 mmol) from Example 20, Step A and 2,2,2-trifluoroacetic acid (487 mg, 4.27 mmol). The reaction mixture was stirred at 80° C. for 8 hours. The CF3COOH was removed under reduced pressure and the residue was purified by column chromatography (Silica gel, DCM/7M NH3 in MeOH from 50/1 to 10/1, v/v) to provide the product (14 mg, 85%). LRMS (APCI−): 100% purity, 220 nm, m/z 377 (M−1) detected; 1H NMR (400 MHz, CD3OD-d4) δ 8.31 (m, 1H), 8.25 (d, J=5.6 Hz, 1H), 7.83 (m, 1H), 7.75 (m, 1H), 7.36 (m, 2H), 7.21 (d, J=8.4 Hz, 1H), 7.04 (m, 1H), 6.28 (d, J=5.6 Hz, 1H), 2.72 (s, 3H)

Workup

customThe CF3COOH was removed under reduced pressure
customthe residue was purified by column chromatography (Silica gel, DCM/7M NH3 in MeOH from 50/1 to 10/1

Sources & evidence

ORD record: ord-9ecee14d62c84190b1bbaccbfd6296e6
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723330B2

Reaction notes

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