Trifluoroacetic acid → 7-[4-(1-Amino-cyclobutyl)-phenyl]-3-chloro-1-methyl-8-phenyl-1H-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-6-one hydrochloride

HRID 1037397Notes

Reaction equation

HRID 1037397 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:48](=[O:68])[C:49]4[C:54]([O:55][C:56]=3[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[C:53]3[N:63]([CH3:67])[N:64]=[C:65]([Cl:66])[C:52]3=[CH:51][CH:50]=4)=[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>[ClH:66].[NH2:36][C:37]1([C:41]2[CH:42]=[CH:43][C:44]([C:47]3[C:48](=[O:68])[C:49]4[C:54]([O:55][C:56]=3[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[C:53]3[N:63]([CH3:67])[N:64]=[C:65]([Cl:66])[C:52]3=[CH:51][CH:50]=4)=[CH:45][CH:46]=2)[CH2:40][CH2:39][CH2:38]1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 510305983-[4-(1-Amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-oneHCID 67067928{1-[4-(3-Chloro-1-methyl-6-oxo-8-phenyl-1,6-dihydro-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 670678557-[4-(1-Amino-cyclobutyl)-phenyl]-3-chloro-1-methyl-8-phenyl-1H-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-6-one hydrochlorideYield 36%

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-(3-chloro-1-methyl-6-oxo-8-phenyl-1,6-dihydro-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester was treated with TFA. The resultant free base was dissolved in a mixture of MeOH (1.5 mL), water (3.5 mL) and 1 M HCl (0.15 mL) and chromatographed on a 2 g C18 cartridge {gradient 30 to 65% MeOH in water+1 M HCl (60 μL in each 5 mL of eluent)} to give the title compound (10 mg, 36%, 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.38 (br s, 3H), 7.82 (d, J=8.6 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.56-7.53 (m, 2H), 7.51-7.44 (m, 3H), 7.41-7.37 (m, 2H), 7.31 (d, J=8.2 Hz, 2H), 4.38 (s, 3H), 2.62-2.49 (m, 4H), 2.22-2.12 (m, 1H), 1.86-1.75 (m, 1H). LCMS (Method E): RT=3.51 min, [M+H]+=456/458.

Workup

  1. customchromatographed on a 2 g C18 cartridge {gradient 30 to 65% MeOH in water+1 M HCl (60 μL in each 5 mL of eluent)}

Sources & evidence

ORD record
ord-c62e301f1a524491bb6c3976df17271b
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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