Acetic Acid → HCID 178446113, compound

HRID 457566Notes

Reaction equation

HRID 457566 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:34])[CH2:9][NH:10][C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[C:12]=2[C:18]2[NH:19][C:20]3[C:25]([N:26]=2)=[C:24]([CH3:27])[N:23]=[C:22]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[N:21]=3)[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.C(O)(=O)C.[CH3:44][CH:45]([CH2:48][CH3:49])[CH:46]=O>C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:34])[CH2:9][NH:10][C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[C:12]=2[C:18]2[NH:19][C:20]3[C:25]([N:26]=2)=[C:24]([CH3:27])[N:23]=[C:22]([N:28]2[CH2:33][CH2:32][N:31]([CH2:44][CH:45]([CH3:46])[CH2:48][CH3:49])[CH2:30][CH2:29]2)[N:21]=3)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 72842-MethylbutanalHCID 178433087HCID 178433087, compound

Product 1

HCID 178446113HCID 178446113, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 4-[2-(3-chloro-phenyl)-2(S)-hydroxy-ethylamino]-3-(6-methyl-2-piperazin-1-yl-9H-purin-8-yl)-1H-pyridin-2-one (20 mg, 0.042 mmol) in a mixture of THF:DMF (1.5 mL:0.5 mL) was added glacial acetic acid (2.3 μl, 0.042 mmol) and 2-methylbutyraldehyde (12 μl, 0.117 mmol). The reaction mixture was stirred at 23° C. for 3 hours followed by the addition of NaBH(OAc) 3 (24.9 mg, 0.117 mmol) to the reaction mixture and stirred for an additional 18 hours. MeOH (0.5 mL) was added and the solution was passed through a SCX cartridge (1 g, 0.79 meq/g, varian). The cartridge was eluted with MeOH (16 mL) and with 2N ammonia in MeOH (16 mL). The ammonia solution was evaporated in vacuo and the solid obtained was purified using a Shimadzu automated preparative HPLC System with the method described below. The solution was evaporated on a Savant Speedvac system to give the title compound as a light yellow solid. (14.2 mg, 62%). HPLC 95%; LCMS (+ESI, M+H+) m/z 551; IR (KBr, cm−1) 3403, 2958, 1645, 1616, 1496, 1233; 1H NMR (400 MHz, DMSO+D2O) δ 10.78 (brs, 1H), 7.60–7.29 (m, 5H), 6.22 (m, 1H), 4.97 (m, 1H), 3.80–3.55 (m, 6H), 2.52–2.15 (m, 8H), 1.75 (brs, 1H), 1.41 (brs, 1H), 1.15 (m, 1H), 0.86 (m, 6H).

Workup

  1. stirringstirred for an additional 18 hours
  2. washThe cartridge was eluted with MeOH (16 mL) and with 2N ammonia in MeOH (16 mL)
  3. customThe ammonia solution was evaporated in vacuo
  4. customthe solid obtained
  5. customwas purified
  6. customThe solution was evaporated on a Savant Speedvac system

Sources & evidence

ORD record
ord-33fe0342617d47ca99c2d48a724df570
Source dataset
uspto-grants-2007_03
Patent number
US07189716B2

Reaction notes

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