Trifluoroacetic acid → HCID 59549923, compound

HRID 1810111Notes

Reaction equation

HRID 1810111 reaction equation
[Cl:1][C:2]1[CH:37]=[CH:36][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])=[CH:22][C:21]=2[C:34]#[N:35])[N:15]=[CH:14]3)=[O:10])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[CH:22][C:21]=2[C:34]#[N:35])[N:15]=[CH:14]3)=[O:10])=[CH:36][CH:37]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68514066HCID 68514066, compound

Product 1

HCID 59549923HCID 59549923, compoundYield 794%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a fitted solution of tert-butyl 2-(4-(5-((4-chlorophenethyl)carbamoyl)-1H-indazol-1-yl)-3-cyanophenyl)acetate (43.4 mg, 0.084 mmol) in DCM (2 mL) was added TFA (250 μL). The reaction was stirred at ambient temperature for 4 hours and then concentrated. The crude product was purified over silica gel on a Biotage Horizon high-performance FLASH chromatography system (12+M silica gel cartridge) eluting with a gradient of 0.5% MeOH/DCM containing 0.5% AcOH to 5% MeOH/DCM containing 0.5% AcOH to give 2-(4-(5-((4-chlorophenethyl)carbamoyl)-1H-indazol-1yl)-3-cyanophenyl)acetic acid (0.038 g, 0.667 mmol, 79%). 1H NMR (400 MHz, CDOD3) δ 8.68 (t, J=5.5 Hz, NH), 8.62 (s, 1H), 8.43 (s, 1H), 8.03 (s, 1H), 7.97 (d J=8.6 Hz, 1H), 7.84 (s, 2H), 7.65 (d, J=8.3 Hz, 1H), 7.35 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.7 Hz, 2H), 3.82 (s, 2H), 3.53 (q. J=6.5 Hz, 2H), 2.88 (t, J=7.3 Hz, 2H). MS(APCI)=459.2 (M+1).

Workup

  1. concentrationconcentrated
  2. customThe crude product was purified over silica gel on a Biotage Horizon high-performance FLASH chromatography system (12+M silica gel cartridge)
  3. washeluting with a gradient of 0.5% MeOH/DCM containing 0.5% AcOH to 5% MeOH/DCM containing 0.5% AcOH

Sources & evidence

ORD record
ord-751db829587e44df871fd30a00a1eb43
Source dataset
uspto-grants-2013_01
Patent number
US08362056B2

Reaction notes

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