Ammonia → HCID 58133687, compound

HRID 707586Notes

Reaction equation

HRID 707586 reaction equation
Br[CH2:2][C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7](=[O:19])[NH:6][CH:5]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[C:4]=1[C:32]([O:34]CC)=O.N.C(#[N:40])C.O>C(#N)C.CO.C(O)(C(F)(F)F)=O.C1COCC1>[O:19]=[C:7]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:17])([F:18])[F:16])[CH:10]=2)[C:3]2[CH2:2][NH:40][C:32](=[O:34])[C:4]=2[CH:5]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[NH:6]1

Participants

8

Reactant 3

HCID 222AmmoniaHCID 18373917Acetonitrile--water (1/1)HCID 58133724HCID 58133724, compound

Product 1

HCID 58133687HCID 58133687, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×HCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

(rac)-Ethyl 6-(bromomethyl)-4-[4-cyano-2-(methylsulfonyl)phenyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (200 mg, 0.34 mmol; Example 13A) was dissolved in acetonitrile (4 ml), a 7 N solution of ammonia in methanol (5 ml) was added and the mixture was stirred at RT for 60 min. The reaction mixture was then concentrated under reduced pressure, and the residue was triturated with acetonitrile (3 ml). The crystals formed were filtered off with suction, washed with acetonitrile and water and, for further purification, separated by preparative HPLC [column: Sunfire C-18, 5 μm, 19 mm×150 mm; sample preparation: the sample was dissolved in 3 ml of acetonitrile+3 ml of 1% strength aqueous TFA solution+2 ml of THF; injection volume: 1000 μl; mobile phase: acetonitrile/water/1% aq. TFA 25:60:15 (0-12 min); flow rate: 25 ml/min; temperature: 40° C.; detection: 210 nm]. This gave 59 mg (36% of theory) of the target compound.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customthe residue was triturated with acetonitrile (3 ml)
  3. customThe crystals formed
  4. filtrationwere filtered off with suction
  5. washwashed with acetonitrile and water and, for further purification
  6. customseparated by preparative HPLC [column
  7. customsample preparation
  8. custom40° C.

Sources & evidence

ORD record
ord-b9a23fb3703f408ca39910ec7214713f
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

Loading…