Hydrochloric Acid → 3-[4-(1-Amino-cyclobutyl)-phenyl]-8-cyclopropyl-2-phenyl-chromen-4-one hydrochloride

HRID 1037283

Reaction equation

HRID 1037283 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]([CH:58]5[CH2:60][CH2:59]5)[CH:52]=[CH:53][CH:54]=4)[O:49][C:48]=3[C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[CH:43][CH:42]=2)[CH2:40][CH2:39][CH2:38]1)(C)(C)C.C(OC(=O)NC1(C2C=CC(C3C(=O)C4C(=C(Br)C=CC=4)OC=3C3C=CC=CC=3)=CC=2)CCC1)(C)(C)C.C(O)(C(F)(F)F)=O.CN1C=C(B2OC(C)(C)C(C)(C)O2)C=N1.C(OC(=O)NC1(C2C=CC(C3C(=O)C4C(=CC(C5NN=CC=5)=CC=4)OC=3C3C=CC=CC=3)=CC=2)CCC1)(C)(C)C.[ClH:166]>CO.O>[ClH:166].[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]([CH:58]5[CH2:60][CH2:59]5)[CH:52]=[CH:53][CH:54]=4)[O:49][C:48]=3[C:61]3[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=3)=[CH:45][CH:46]=2)[CH2:40][CH2:39][CH2:38]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 510305983-[4-(1-Amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-oneHCID 67067641(1-{4-[4-oxo-2-phenyl-7-(2H-pyrazol-3-yl)-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterHCID 67067700{1-[4-(8-Bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterHCID 67067900{1-[4-(8-Cyclopropyl-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 670677983-[4-(1-Amino-cyclobutyl)-phenyl]-8-cyclopropyl-2-phenyl-chromen-4-one hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Following the procedure used to prepare 3-[4-(1-amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-one, a mixture containing 70% {1-[4-(8-cyclopropyl-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester and 30% {1-[4-(8-bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester was treated with TFA. The resultant free base was reacted with 1-methylpyrazole-4-boronic acid pinacol ester following the procedure of (1-{4-[4-oxo-2-phenyl-7-(2H-pyrazol-3-yl)-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester. The combined products were dissolved in a mixture of MeOH (7 mL), water (7 mL) and 1 M HCl (0.6 mL) and chromatographed on a 5 g C18 cartridge {gradient 10 to 90% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)} to give the title compound as a white solid (11 mg). 1H NMR (300 MHz, DMSO-d6): δ 8.60 (s, 3H), 7.91 (dd, J=7.1 and 2.4 Hz, 1H), 7.52-7.27 (m, 11H), 2.65-2.47 (m, 4H), 2.45-2.34 (m, 1H), 2.26-2.09 (m, 1H), 1.88-1.73 (m, 1H), 1.14-1.04 (m, 2H), 0.90-0.82 (m, 2H). LCMS (Method E): RT=4.01 min, [M+H]+=408. 3-[4-(1-amino-cyclobutyl)-phenyl]-8-(1-methyl-1H-pyrazol-4-yl)-2-phenyl-chromen-4-one hydrochloride was also isolated.

Workup

  1. customchromatographed on a 5 g C18 cartridge {gradient 10 to 90% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)}

Sources & evidence

ORD record
ord-ca76497a531e44f393ad61e5e4ecec28
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Linked notes

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