2-Hydroxyisobutyric acid → HCID 59605285, compound

HRID 1923335Notes

Reaction equation

HRID 1923335 reaction equation
[CH3:1][C:2]1([CH3:36])[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[CH2:8][C:9]1[N:10]([CH3:35])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH2:33][CH3:34])[N:12]=2.[OH:37][C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:33]([C:25]1[N:24]([C:13]2[N:12]=[C:11]3[C:16]([N:17]=[C:9]([CH2:8][N:3]4[CH2:4][CH2:5][N:6]([C:39](=[O:40])[C:38]([OH:37])([CH3:43])[CH3:42])[CH2:7][C:2]4([CH3:1])[CH3:36])[N:10]3[CH3:35])=[C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:14]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=1)[CH3:34]

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 67492830HCID 67492830, compound

Product 1

HCID 59605285HCID 59605285, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 8-(2,2-dimethylpiperazin-1-ylmethyl)-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.20 mmol), 2-hydroxyisobutyric acid (24 mg, 0.23 mmol), HATU (85 mg, 0.22 mmol) and DIPEA (40 μL, 0.23 mmol) in DCM (2 mL) was allowed to stir at r.t. for 17 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-3%) affording 741 as a white solid (55 mg, 46%). LCMS (method I): RT 2.89 min, [M+H]+ 576.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-8.02 (1 H, m), 7.76-7.75 (1 H, m), 7.33-7.22 (2 H, m), 4.40-4.20 (5 H, m), 3.92 (3 H, s), 3.88-3.83 (5 H, m), 3.63 (2 H, s), 3.53 (2 H, s), 3.36 (2 H, q, J=7.48 Hz), 2.59-2.53 (2 H, m), 1.50 (6 H, s), 1.45 (3 H, t, J=7.48 Hz), 1.23 (6 H, s)

Workup

  1. washwas washed with MeOH
  2. washthe product eluted with 2M NH3/MeOH
  3. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-3%)

Sources & evidence

ORD record
ord-b37b2249ad414d59bc56206a0af2504d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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