Trifluoroacetic acid → 4-({2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-[2,2-difluorocyclopropyl]propanoyl}amino)benzoic acid

HRID 57022Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:40]#[N:41])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:33][CH:34]3[CH2:36][C:35]3([F:38])[F:37])[C:17]([NH:19][C:20]3[CH:32]=[CH:31][C:23]([C:24]([O:26]C(C)(C)C)=[O:25])=[CH:22][CH:21]=3)=[O:18])[C:10](=[O:39])[CH:9]=2)[CH:7]=1.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:40]#[N:41])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:33][CH:34]3[CH2:36][C:35]3([F:38])[F:37])[C:17]([NH:19][C:20]3[CH:32]=[CH:31][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=3)=[O:18])[C:10](=[O:39])[CH:9]=2)[CH:7]=1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 117622852HCID 117622852, compound

Product 1

HCID 862979494-({2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-[2,2-difluorocyclopropyl]propanoyl}amino)benzoic acid

Procedure

74.0 mg (127 μmol) of tert-butyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-[2,2-difluorocyclopropyl]propanoyl}amino)benzoate (mixture of racemic diastereomers) and 195 μl (2.53 mmol) of TFA were reacted according to General Method 2. The crude product was purified by preparative HPLC [column: Chromatorex C18, 10 μm, 125 mm×30 mm, mobile phase: acetonitrile/water gradient (0 to 3 min 15% acetonitrile, to 35 min 90% acetonitrile and a further 3 min 90% acetonitrile)]. Yield: 45 mg (52% of theory)

Workup

customThe crude product was purified by preparative HPLC [column
customa further 3 min 90% acetonitrile

Sources & evidence

ORD record: ord-3021c11e315e4e229b6cceca6d0fd7a1
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434690B2

Reaction notes

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