Propionic Acid → N-((S)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO[3,2-D]PYRIMIDIN-4-YL}-PYRROLIDIN-2-YLMETHYL)-PROPIONAMIDE

HRID 70115Notes

Reaction equation

HRID 70115 reaction equation
[C:1]([OH:5])(=O)[CH2:2][CH3:3].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[Cl:46][C:47]1[CH:52]=[CH:51][C:50]([N:53]2[CH2:58][CH2:57][N:56]([C:59]3[N:60]=[C:61]([N:69]4[CH2:73][CH2:72][CH2:71][C@H:70]4[CH2:74][NH2:75])[C:62]4[S:67](=[O:68])[CH2:66][CH2:65][C:63]=4[N:64]=3)[CH2:55][CH2:54]2)=[CH:49][CH:48]=1>CS(C)=O.ClCCl.O>[Cl:46][C:47]1[CH:52]=[CH:51][C:50]([N:53]2[CH2:54][CH2:55][N:56]([C:59]3[N:60]=[C:61]([N:69]4[CH2:73][CH2:72][CH2:71][C@H:70]4[CH2:74][NH:75][C:1](=[O:5])[CH2:2][CH3:3])[C:62]4[S:67](=[O:68])[CH2:66][CH2:65][C:63]=4[N:64]=3)[CH2:57][CH2:58]2)=[CH:49][CH:48]=1

Participants

8

Reactant 4

HCID 1032Propionic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66735925HCID 66735925, compound

Product 1

HCID 59708458N-((S)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO[3,2-D]PYRIMIDIN-4-YL}-PYRROLIDIN-2-YLMETHYL)-PROPIONAMIDE

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

17 μl propionic acid are placed in 800 μl dimethylsulphoxide, and 78 μl diisopropylethylamine and 94 mg O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) are added. The mixture is stirred for 0.3 hours at ambient temperature, then a solution of 100 mg C—((S)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-pyrrolidin-2-yl)-methylamine trifluoroacetate, Diastereomer 2 (Example 226) (see scheme 3, 3.17.2), in 700 μl dimethylsulphoxide is added. The reaction mixture is stirred for 15 hours at ambient temperature and then combined with water and dichloromethane. The organic phase is dried and evaporated to dryness. The product is purified by preparative HPLC (method A). 84 mg of the product are obtained as an oil. Analytical HPLC-MS (method D): RT=1.19 min.

Workup

  1. stirringThe reaction mixture is stirred for 15 hours at ambient temperature
  2. customThe organic phase is dried
  3. customevaporated to dryness
  4. customThe product is purified by preparative HPLC (method A)

Sources & evidence

ORD record
ord-7c64befe1f614bd78decddb6d416772f
Source dataset
uspto-grants-2014_09
Patent number
US08822474B2

Reaction notes

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