Trifluoroacetic acid → HCID 89601244, compound

HRID 869081Notes

Reaction equation

HRID 869081 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:18]2[CH:25]([C:26]3[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[C:28]([F:34])[CH:27]=3)[C:24]3[C:20](=[N:21][N:22]([C:38]4[C:39]([O:47][CH3:48])=[N:40][C:41]([N:44]([CH3:46])[CH3:45])=[N:42][CH:43]=4)[C:23]=3[CH:35]([CH3:37])[CH3:36])[C:19]2=[O:49])[C:5](=[O:17])[N:6](CC2C=CC(OC)=CC=2)[CH:7]=1.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([N:18]2[CH:25]([C:26]3[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[C:28]([F:34])[CH:27]=3)[C:24]3[C:20](=[N:21][N:22]([C:38]4[C:39]([O:47][CH3:48])=[N:40][C:41]([N:44]([CH3:45])[CH3:46])=[N:42][CH:43]=4)[C:23]=3[CH:35]([CH3:37])[CH3:36])[C:19]2=[O:49])[C:5](=[O:17])[NH:6][CH:7]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 91801091HCID 91801091, compound

Product 1

HCID 89601244HCID 89601244, compoundYield 37.9%

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(5-(5-chloro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-(2-(dimethylamino)-4-methoxypyrimidin-5-yl)-3-isopropyl-6-oxo-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-4-yl)-2-fluorobenzonitrile (388 mg, 0.568 mmol, product from step 193.1) and TFA (2.188 ml, 28.4 mmol) was stirred at 100° C. for 1 hour. Then the reaction mixture was quenched with a saturated NaHCO3 solution and extracted twice with CH2Cl2. The organic layers were combined and washed with saturated NaHCO3 solution, dried (Na2SO4) and evaporated. The reaction mixture was purified by chromatography (Silicagel, EtOAc). After evaporation of the fractions, the residue was triturated in diisopropylether to afford 121 mg (0.215 mmol, 37.8% yield) of the title compound as a white solid. LCMS: (M+H)=563/565; tR=1.04 min (LC−MS 4). TLC: Rf=0.34 (EtOAc). 1H−NMR (DMSO−d6, 600 MHz) δ ppm 12.36 (s, 1H) 8.28 (s, 1H) 7.91 (t, 1H) 7.65−7.53 (m, 3H) 7.40 (d, 1H) 6.84 (bs, 1H) 3.87 (s, 3H) 3.18 (s, 6H) 2.60 (m, 1H) 1.08 (d, 3H) 0.47 (d, 3H).

Workup

  1. customThen the reaction mixture was quenched with a saturated NaHCO3 solution
  2. extractionextracted twice with CH2Cl2
  3. washwashed with saturated NaHCO3 solution
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe reaction mixture was purified by chromatography (Silicagel, EtOAc)
  7. customAfter evaporation of the fractions
  8. customthe residue was triturated in diisopropylether

Sources & evidence

ORD record
ord-eb2bcecf7680484da75549a828a89fba
Source dataset
uspto-grants-2015_03
Patent number
US08969341B2

Reaction notes

Loading…