Isobutyric Acid → HCID 66803363, compound

HRID 341452Notes

Reaction equation

HRID 341452 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.[NH2:43][CH:44]1[CH2:49][CH2:48][CH:47]([C:50]2[O:54][N:53]=[C:52]([C:55]3[N:60]=[C:59]([N:61]([CH3:68])[C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)[N:58]=[C:57]([NH2:69])[N:56]=3)[N:51]=2)[CH2:46][CH2:45]1>CN(C=O)C>[NH2:69][C:57]1[N:58]=[C:59]([N:61]([CH3:68])[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[N:60]=[C:55]([C:52]2[N:51]=[C:50]([CH:47]3[CH2:48][CH2:49][CH:44]([NH:43][C:3](=[O:5])[CH:2]([CH3:6])[CH3:1])[CH2:45][CH2:46]3)[O:54][N:53]=2)[N:56]=1

Participants

6

Reactant 4

HCID 6590Isobutyric AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66802769HCID 66802769, compound

Product 1

HCID 66803363HCID 66803363, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-methylpropanoic acid (0.03 g, 0.327 mmol) in DMF (5 mL) was added DIPEA (0.122 mL, 0.682 mmol) followed by (1H-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (0.13 g, 0.3 mmol). The reaction mixture was stirred at room temperature for 5 min and 6-[5-(4-aminocyclohexyl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine (batch 1 from Example 422, 0.1 g, 0.273 mmol) was added. The reaction mixture was stirred at room temperature for 16 h and then concentrated, extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated. The residue was purified by FCC, eluting with 0-10% MeOH in DCM. The crude product was dissolved in EtOAc, washed with saturated aq. sodium bicarbonate, dried over sodium sulfate and concentrated under vacuum to afford the title compound (0.0255 g, 21%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 16 h
  2. concentrationconcentrated
  3. extractionextracted with EtOAc
  4. washwashed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by FCC
  8. washeluting with 0-10% MeOH in DCM
  9. dissolutionThe crude product was dissolved in EtOAc
  10. washwashed with saturated aq. sodium bicarbonate
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-f96eb32812a54c2082ae2d6659f395e5
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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