(S)-3-hydroxybutyric acid → (2S)-4-{4-[2-(2-Aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]piperazin-1-yl}-4-oxobutan-2-ol

HRID 1876569

Reaction equation

HRID 1876569 reaction equation
[OH:1][C@@H:2]([CH3:7])[CH2:3][C:4]([OH:6])=O.O.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=NCCCN(C)C)C.FC(F)(F)C(O)=O.[N:38]1([C:44]2[N:52]=[C:51]([C:53]3[CH:54]=[N:55][C:56]([NH2:59])=[N:57][CH:58]=3)[N:50]=[C:49]3[C:45]=2[N:46]=[C:47]([N:65]2[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]2)[N:48]3[CH2:60][C:61]([F:64])([F:63])[F:62])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C(N(CC)CC)C.CN(C)C=O>[NH2:59][C:56]1[N:57]=[CH:58][C:53]([C:51]2[N:50]=[C:49]3[C:45]([N:46]=[C:47]([N:65]4[CH2:70][CH2:69][N:68]([C:4](=[O:6])[CH2:3][C@@H:2]([OH:1])[CH3:7])[CH2:67][CH2:66]4)[N:48]3[CH2:60][C:61]([F:62])([F:64])[F:63])=[C:44]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[N:52]=2)=[CH:54][N:55]=1

Participants

7

Reactant 4

HCID 94318(S)-3-hydroxybutyric acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866419965-[6-Morpholin-4-yl-8-piperazin-1-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine trifluoroacetateHCID 178526939HCID 178526939, compound

Product 1

HCID 59333531(2S)-4-{4-[2-(2-Aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]piperazin-1-yl}-4-oxobutan-2-olYield 50.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(S)-3-hydroxybutanoic acid (39 mg, 0.38 mmol), hydroxybenzotriazole hydrate (58 mg, 0.38 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (72 mg, 0.38 mmol), dimethylformamide (5 ml), and triethylamine (161 μl) were added to 5-[6-morpholin-4-yl-8-piperazin-1-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine trifluoroacetate (200 mg, 0.29 mmol) and the resulting mixture was stirred for 15 hours. The reaction mixture was partitioned with ethyl acetate and saturated aqueous sodium bicarbonate solution, the organic layer was dried over magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (chloroform:methanol=19:1) to give the title compound (80 mg, 50%) as a white solid.

Workup

  1. customThe reaction mixture was partitioned with ethyl acetate and saturated aqueous sodium bicarbonate solution
  2. dry with materialthe organic layer was dried over magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-ac8fb76feb154a72acbc552d77c4fce2
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Linked notes

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