Trifluoroacetic acid → 3-[4-(1-Amino-cyclobutyl)-phenyl]-7-methoxy-2-phenyl-8-(1H-pyrazol-4-yl)-chromen-4-one

HRID 1037346Notes

Reaction equation

HRID 1037346 reaction equation
NC1(C2C=CC(C3C(=O)C4C(=CC=C(F)C=4)OC=3C3C=CC=CC=3)=CC=2)CCC1.C(OC(=O)[NH:36][C:37]1([C:41]2[CH:46]=[CH:45][C:44]([C:47]3[C:56](=[O:57])[C:55]4[C:50](=[C:51]([C:60]5[CH:61]=[N:62][NH:63][CH:64]=5)[C:52]([O:58][CH3:59])=[CH:53][CH:54]=4)[O:49][C:48]=3[C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:43][CH:42]=2)[CH2:40][CH2:39][CH2:38]1)(C)(C)C.C(O)(C(F)(F)F)=O>CO.O.Cl>[NH2:36][C:37]1([C:41]2[CH:42]=[CH:43][C:44]([C:47]3[C:56](=[O:57])[C:55]4[C:50](=[C:51]([C:60]5[CH:64]=[N:63][NH:62][CH:61]=5)[C:52]([O:58][CH3:59])=[CH:53][CH:54]=4)[O:49][C:48]=3[C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:45][CH:46]=2)[CH2:38][CH2:39][CH2:40]1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 510305983-[4-(1-Amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-oneHCID 67067864(1-{4-[7-Methoxy-4-oxo-2-phenyl-8-(1H-pyrazol-4-yl)-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester

Product 1

HCID 510302343-[4-(1-Amino-cyclobutyl)-phenyl]-7-methoxy-2-phenyl-8-(1H-pyrazol-4-yl)-chromen-4-oneYield 34.3%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Following the procedure used to prepare 3-[4-(1-amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-one, (1-{4-[7-methoxy-4-oxo-2-phenyl-8-(1H-pyrazol-4-yl)-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester (50 mg, 0.088 mmol) was treated with TFA. The resultant free base was dissolved in a mixture of MeOH (7 mL), water (7 mL) and 1 M HCl (0.6 mL) and chromatographed on a 20 g C18 cartridge {gradient 30 to 80% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)} to yield the title compound as a white solid (14 mg, 32%). 1H NMR (300 MHz, DMSO-d6): δ 8.75 (s, 3H), 8.12-8.01 (m, 3H), 7.50-7.24 (m, 9H), 7.11 (s, 1H), 4.01 (s, 3H), 2.62-2.48 (m, 4H), 2.27-2.10 (m, 1H), 1.87-1.72 (m, 1H). LCMS (Method E): RT=2.99 min, [M+H]+=464.

Workup

  1. customchromatographed on a 20 g C18 cartridge {gradient 30 to 80% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)}

Sources & evidence

ORD record
ord-6807d93f2db1433ab9d744f3bd0937df
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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