Triethylamine → 4-(2,5-Dioxo-3-(2-oxo-2-thiomorpholinoethyl)-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)benzonitrile

HRID 927219Notes

Reaction equation

HRID 927219 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]([CH2:15][C:16]([OH:18])=O)[C:13](=[O:19])[N:12]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=3)[C:11]3[CH2:30][CH2:31][C:32](=[O:33])[C:10]2=3)=[CH:5][CH:4]=1)#[N:2].C(N(CC)CC)C.F[B-](F)(F)F.C[N+](C)=C(N(C)C)ON1C2C=CC=CC=2N=N1.[NH:63]1[CH2:68][CH2:67][S:66][CH2:65][CH2:64]1>CN(C)C=O>[O:19]=[C:13]1[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:28])([F:27])[F:29])[CH:21]=2)[C:11]2[CH2:30][CH2:31][C:32](=[O:33])[C:10]=2[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=2)[N:14]1[CH2:15][C:16](=[O:18])[N:63]1[CH2:68][CH2:67][S:66][CH2:65][CH2:64]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 67164ThiomorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 903109622-(4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-6,7-dihydro-1H-cyclopenta[d]pyrimidin-3(2H,4H,5H)-yl)acetic acid

Product 1

HCID 903112034-(2,5-Dioxo-3-(2-oxo-2-thiomorpholinoethyl)-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 2-(4-(4-cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-6,7-dihydro-1H-cyclopenta[d]pyrimidin-3(2H,4H,5H)-yl)acetic acid (example 4, 30 mg, 66 μmol) and triethylamine (30 μL, 0.22 mmol) in N,N-dimethylformamide (1.25 mL) is treated with N,N,N′,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (21 mg, 66 μmol) and stirred at room temperature for 15 min. This mixture is then added to a solution of thiomorpholine (13 mg, 0.13 mmol) in N,N-dimethylformamide (0.25 mL) and stirred for 72 h. The mixture is filtered and the filtrate is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of methanol in water, 0.1% NH3). Yield: 20 mg; ESI mass spectrum [M+H]+=541; Retention time HPLC: 1.17 min (001_CA03).

Workup

  1. stirringstirred for 72 h
  2. filtrationThe mixture is filtered
  3. customthe filtrate is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of methanol in water, 0.1% NH3)
  4. custom1.17 min (001_CA03)

Sources & evidence

ORD record
ord-27e9a7e481af443cb9f44b94f8aac422
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

Loading…