Potassium Iodide → HCID 66601835, compound

HRID 707623Notes

Reaction equation

HRID 707623 reaction equation
Cl.Cl[CH2:3][C:4]1[N:5]=[CH:6][S:7][CH:8]=1.[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:20]2[C:25]([C:26]#[N:27])=[C:24]([CH3:28])[N:23]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=3)[C:22](=[O:39])[N:21]2[CH3:40])=[C:15]([S:17]([O-:19])=[O:18])[CH:16]=1)#[N:10].[Na+].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C>[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:20]2[C:25]([C:26]#[N:27])=[C:24]([CH3:28])[N:23]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=3)[C:22](=[O:39])[N:21]2[CH3:40])=[C:15]([S:17]([CH2:3][C:4]2[N:5]=[CH:6][S:7][CH:8]=2)(=[O:19])=[O:18])[CH:16]=1)#[N:10]

Participants

7

Reactant 5

HCID 4875Potassium Iodide2×HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 27632894-(Chloromethyl)-1,3-thiazole hydrochloride2×HCID 66924241Sodium 5-cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfinate

Product 1

HCID 66601835HCID 66601835, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

The reaction was carried out under argon. 4-(Chloromethyl)thiazole hydrochloride (86 mg, 505 μmol; 5.0 eq.), sodium 5-cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfinate (150 mg, 101 μmol; purity 32%), potassium carbonate (77 mg, 556 μmol; 5.5 eq.), potassium iodide (84 mg, 505 μmol; 5.0 eq.) and 18-crown-6 (13.4 mg, 51 μmol; 0.5 eq.) were suspended in DMF (3 ml). The mixture was then heated in a closed tube at 110° C. for 15 h. Molecular sieve (4 Å), potassium iodide (84 mg, 505 μmol; 5.0 eq.) and further 4-(chloromethyl)thiazole hydrochloride (86 mg, 505 μmol; 5.0 eq.) were then added, and the reaction mixture was again heated in a closed tube at 100° C. for 2 h. The mixture was then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The title compound was obtained as a solid (37 mg, 66% of theory).

Workup

  1. temperaturethe reaction mixture was again heated in a closed tube at 100° C. for 2 h
  2. filtrationThe mixture was then filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)

Sources & evidence

ORD record
ord-5dc0f3cec07645f79ad197a02ffe122c
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

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