Isobutyric Acid → HCID 66802656, compound

HRID 341421Notes

Reaction equation

HRID 341421 reaction equation
[CH3:1][CH:2]([CH3:6])[C:3]([OH:5])=O.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[CH3:44][N:45]([C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C:46]1[N:51]=[C:50]([NH2:52])[N:49]=[C:48]([C:53]2[N:57]=[C:56]([CH:58]3[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]3)[O:55][N:54]=2)[N:47]=1>CN(C=O)C.O>[NH2:52][C:50]1[N:51]=[C:46]([N:45]([CH3:44])[C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=2)[N:47]=[C:48]([C:53]2[N:57]=[C:56]([CH:58]3[CH2:63][CH2:62][N:61]([C:3](=[O:5])[CH:2]([CH3:6])[CH3:1])[CH2:60][CH2:59]3)[O:55][N:54]=2)[N:49]=1

Participants

7

Reactant 4

HCID 6590Isobutyric AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66802903HCID 66802903, compound2×

Product 1

HCID 66802656HCID 66802656, compoundYield 91.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 2-methylpropanoic acid (27.0 μL, 0.299 mmol) in DMF (5 mL) was added DIPEA (109 μL, 0.624 mmol) at room temperature and the mixture was stirred for 5 min. (1H-Benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (0.121 g, 0.274 mmol) was added to the reaction mixture and stirred for 5 min. 2-N-Methyl-2-N-phenyl-6-[5-(piperidin-4-yl)-1,2,4-oxadiazol-3-yl]-1,3,5-triazine-2,4-diamine hydrochloride (Intermediate 105, 0.100 g, 0.249 mmol) was added and the mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with water, extracted with EtOAc and the organic layer washed with brine. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude compound was purified by FCC (DCM:MeOH 90:10) to afford the title compound (96 mg, 88%).

Workup

  1. additionwas added to the reaction mixture
  2. stirringthe mixture was stirred at room temperature for 18 h
  3. extractionextracted with EtOAc
  4. washthe organic layer washed with brine
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude compound was purified by FCC (DCM:MeOH 90:10)

Sources & evidence

ORD record
ord-f515710e11df4a289263652468546f46
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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