Acetic Acid → HCID 178480955, compound

HRID 432349Notes

Reaction equation

HRID 432349 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH:31](=O)[C:32]1[O:36][CH:35]=[CH:34][CH:33]=1.[C:38]([OH:41])(=O)[CH3:39].C(O[BH-](O[C:52](=O)[CH3:53])OC(=O)C)(=O)C.[Na+].[C:56](=O)(O)[O-].[Na+]>ClC(Cl)C>[O:41]1[CH:53]=[CH:52][CH:56]=[C:38]1[CH2:39][N:1]([CH2:31][C:32]1[O:36][CH:35]=[CH:34][CH:33]=1)[C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7362FurfuralHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178480953HCID 178480953, compound

Product 1

HCID 178480955HCID 178480955, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of cis-3-(3-aminophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.120 g, 0.296 mmol, 1 equiv), furfural (0.03 mL, 0.3 mmol, 1.1 equiv), glacial acetic acid (0.07 mL, 1.1 mmol, 3.8 equiv), and sodium triacetoxyborohydride (0.314 g, 1.48 mmol, 5.0 equiv) in dichloroethane (2 mL) was stirred at ambient temperature for 60 h. Saturated aqueous sodium bicarbonate solution (5 mL) was added, the organic layer was separated, and the aqueous layer was extracted with two portions of CH2Cl2 (10 mL each). The organic extracts were dried over MgSO4, filtered, and concentrated to afford a yellow oil. Purification by column chromatography on silica gel (elution with 200 mL of 5% MeOH/CH2Cl2, 100 mL of 10% MeOH/CH2Cl2, and 300 mL of 10:20:70% MeOH/Et3N/CH2Cl2) afforded cis-3-{3-[di(2-furylmethyl)amino]phenyl}-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.051 g, 0.10 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.22 (1H, s), 7.60 (2H, s), 7.31-7.35 (1H, m), 7.19 (1H, s), 7.00 (1H, d, J=8.4 Hz), 6.93 (1H, d, J=7.6 Hz), 6.39 (2H, s), 6.32 (2H, s), 4.77-4.80 (1H, m), 4.60 (4H, s), 2.23-2.39 (11H, m), 2.16 (3H, s), 2.05-2.07 (2H, m), 1.59-1.71 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 14.52 min. MS: MH+ 567.

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with two portions of CH2Cl2 (10 mL each)
  3. dry with materialThe organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a yellow oil
  7. customPurification by column chromatography on silica gel (elution with 200 mL of 5% MeOH/CH2Cl2, 100 mL of 10% MeOH/CH2Cl2, and 300 mL of 10:20:70% MeOH/Et3N/CH2Cl2)

Sources & evidence

ORD record
ord-eb4b2ce95bbf49d5b25f782d7164e827
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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