Acetic Acid → HCID 178461902, compound

HRID 243300Notes

Reaction equation

HRID 243300 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.[O:28]1[CH2:31][C:30](=O)[CH2:29]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[O:28]1[CH2:31][CH:30]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[N:9]=[C:8]3[C@@H:16]([NH:18][C:19]3[N:27]=[CH:26][N:25]=[C:24]4[C:20]=3[N:21]=[CH:22][NH:23]4)[CH3:17])[CH2:3][CH2:2]2)[CH2:29]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 178461903HCID 178461903, compound

Product 1

HCID 178461902HCID 178461902, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of (S)—N-(1-(1-(piperidin-4-yl)-1H-benzo[d]imidazol-2-yl)ethyl)-9H-purin-6-amine from Example 113 (99 mg, 0.273 mmol) in anhydrous DCE (10 mL) was added oxetan-3-one (32 μL, 0.546 mmol) followed by AcOH (16 μL, 0.273 mmol) and 4 Å (angstrom) powdered molecular sieves (0.1 g). After stirring for 4 h, sodium triacetoxyborohydride (116 mg, 0.546 mmol) was added and stirring was continued for 48 h. The crude reaction mixture was loaded into an Isolute® SCX-2 which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) and then triturated with diethyl ether and MeOH affording 129 as a white solid (50 mg, 44%). LCMS: RT 1.61 min [M+H]+ 419.1. 1H NMR (DMSO, 400 MHz, 80° C.): δ 8.25 (1H, s), 8.05 (1H, s), 7.65-7.59 (2H, m), 7.44 (1H, bs), 7.20-7.13 (2H, m), 6.16-6.04 (1H, m), 4.63-4.39 (6H, m), 3.50-3.42 (1H, m), 2.93-2.85 (1H, bd, J=10.45 Hz), 2.76-2.69 (1H, bd, J=10.45 Hz), 2.40-2.28 (1H, m), 2.04-1.93 (1H, t, J=11.60 Hz), 1.90-1.81 (1H, m), 1.76-1.53 (6H, m)

Workup

  1. stirringstirring
  2. waitwas continued for 48 h
  3. customThe crude reaction mixture
  4. washwas washed with MeOH
  5. washthe product eluted with 2M NH3/MeOH
  6. additionThe product containing fractions
  7. concentrationconcentrated in vacuo
  8. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  9. customtriturated with diethyl ether and MeOH affording 129 as a white solid (50 mg, 44%)

Sources & evidence

ORD record
ord-12af4bed73dc4a3e86fac501c2222939
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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