2-Hydroxyisobutyric acid → HCID 178461905, compound

HRID 243292Notes

Reaction equation

HRID 243292 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:3][CH2:2]1.[OH:28][C:29]([CH3:34])([CH3:33])[C:30](O)=[O:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:27]1[C:19]([NH:18][C@H:16]([C:8]2[N:7]([CH:4]3[CH2:5][CH2:6][N:1]([C:30](=[O:31])[C:29]([OH:28])([CH3:34])[CH3:33])[CH2:2][CH2:3]3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH3:17])=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

6

Reactant 4

HCID 116712-Hydroxyisobutyric acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178461903HCID 178461903, compound

Product 1

HCID 178461905HCID 178461905, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(S)-1-(1-piperidin-4-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine 113 (97 mg, 0.268 mmol) in DMF (5 mL) were added 2-hydroxy-2-methylpropionic acid (31 mg, 0.294 mmol), DIPEA (230 μL, 1.34 mmol) and HATU (153 mg, 0.401 mmol). Stirring at RT was continued for 18 h then the crude reaction mixture was partitioned between EtOAc and a saturated solution of NaHCO3. The organic layer was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 121 as a pale beige solid (33 mg, 31%). LCMS: RT 2.28 min [M+H]+ 449.1. 1H NMR (CDCl3, 400 MHz): δ 8.51 (1H, s), 7.98 (1H, s), 7.79 (1H, d, J=7.80 Hz), 7.36-6.99 (4H, m), 5.32 (1H, bs), 5.02-4.88 (2H, m), 4.78 (1H, bs), 4.59-4.49 (1H, br), 2.64-2.44 (2H, m), 2.37-2.22 (1H, m), 2.05 (1H, d, J=12.70 Hz), 2.95-1.49 (11H, m)

Workup

  1. customthe crude reaction mixture
  2. customwas partitioned between EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-d0dc58b7a6084ba985f243811262e242
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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