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 1911066Notes

Reaction equation

HRID 1911066 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 32 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-ba9e1f9623164a4daa6139bfed0e4621
Source dataset
uspto-grants-2013_12
Patent number
US08604039B2

Reaction notes

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