Formic Acid → azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926630Notes

Reaction equation

HRID 926630 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([C:12]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25]([O:30][CH3:31])[C:24]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=2)=[C:23]3[Cl:43])([OH:19])[C:13]2[N:17]([CH3:18])[N:16]=[N:15][CH:14]=2)[CH2:9]1)=O)(C)(C)C.C(O)=O.Cl>CO>[NH:8]1[CH2:11][CH:10]([C:12]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25]([O:30][CH3:31])[C:24]([CH2:32][C:33]2[CH:34]=[CH:35][C:36]([C:39]([F:41])([F:40])[F:42])=[CH:37][CH:38]=2)=[C:23]3[Cl:43])([C:13]2[N:17]([CH3:18])[N:16]=[N:15][CH:14]=2)[OH:19])[CH2:9]1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 86715661tert-Butyl-3-((4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(hydroxy)(1-methyl-1H-1,2,3-triazol-5-yl)methyl)azetidine-1-carboxylate

Product 1

HCID 86715675azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a flask containing tert-butyl 3-((4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(hydroxy)(1-methyl-1H-1,2,3-triazol-5-yl)methyl)azetidine-1-carboxylate (165 mg, 0.27 mmol, Example 123) was added formic acid (5 mL) at room temperature followed by 6 N aqueous HCl (0.21 mL). The mixture was stirred at room temperature for 40 minutes and then MeOH (5 mL) was added and the mixture was stirred for 20 minutes before concentrating. The resulting oil was chromatographed directly on silica gel (10% 2 M NH3-MeOH-DCM increasing to 12% 2 M NH3-MeOH) to provide the title compound as an off white powder. 1H NMR (500 MHz, CDCl3) δ 8.30 (d, J=2.1 Hz, 1H), 8.20 (s, 1H), 7.92 (s, 1H), 7.76 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.1 Hz, 2H), 7.42-7.32 (m, 3H), 4.52-4.34 (m, 2H), 4.33-4.16 (m, 3H), 4.05 (s, 3H), 3.96-3.80 (m, 1H), 3.71 (s, 4H); MS (ESI): mass calcd. Chemical Formula: C25H23ClF3N5O2; Exact Mass: 517.2. m/z found 517.9 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 20 minutes
  2. concentrationbefore concentrating
  3. customThe resulting oil was chromatographed directly on silica gel (10% 2 M NH3-MeOH-DCM increasing to 12% 2 M NH3-MeOH)

Sources & evidence

ORD record
ord-8586eeaa791d43c48301d1fb9973dd91
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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