Diisopropylethylamine → HCID 66602058, compound

HRID 336930Notes

Reaction equation

HRID 336930 reaction equation
[C:1]([C:3]1[C@@H:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=2[S:17]([CH3:20])(=[O:19])=[O:18])[N:7]([CH2:21][C:22](O)=[O:23])[C:6](=[O:25])[N:5]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)[C:4]=1[CH3:36])#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:61]=[C:62]1[CH2:67][NH:66][CH2:65][CH2:64][NH:63]1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([C@@H:8]2[C:3]([C:1]#[N:2])=[C:4]([CH3:36])[N:5]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=3)[C:6](=[O:25])[N:7]2[CH2:21][C:22](=[O:23])[N:66]2[CH2:65][CH2:64][NH:63][C:62](=[O:61])[CH2:67]2)=[C:10]([S:17]([CH3:20])(=[O:18])=[O:19])[CH:11]=1)#[N:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 42640886HCID 42640886, compound

Product 1

HCID 66602058HCID 66602058, compoundYield 55.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The reaction was carried out under argon. 2-[(6S)-5-Cyano-6-[4-cyano-2-(methylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]acetic acid (50 mg, 96 μmol; Example 21) was initially charged in DMF (2 ml), HATU (183 mg, 482 μmol, 5 eq.) was added at 0° C. and the mixture was stirred for 20 min. 2-Oxopiperazine (48.3 mg, 482 μmol, 5 eq.) and N,N-diisopropylethylamine (62 mg, 482 μmol, 5 eq.) were then added, and the mixture was stirred at RT for 30 min until complete conversion had been achieved (HPLC control). The reaction mixture was then concentrated under reduced pressure and the crude product was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave the title compound as a colorless solid (32 mg, 55% of theory).

Workup

  1. stirringthe mixture was stirred at RT for 30 min until complete conversion
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. customthe crude product 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-51faf4ddfcb24ea2a9bec931b7ddaca2
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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