Acetic Acid → HCID 178476627, compound

HRID 432348Notes

Reaction equation

HRID 432348 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.[C:31]([OH:34])(=[O:33])[CH3:32].[O:35]1[C:39]([CH:40]=O)=[CH:38][C:37]2[CH:42]=[CH:43][CH:44]=[CH:45][C:36]1=2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClC(Cl)C.C(=O)(O)[O-].[Na+]>>[C:31]([OH:34])(=[O:33])[CH3:32].[O:35]1[C:39]([CH2:40][NH:1][C:2]2[CH:3]=[C:4]([C:8]3[C:16]4[C:11](=[N:12][CH:13]=[N:14][C:15]=4[NH2:17])[N:10]([C@H:18]4[CH2:23][CH2:22][C@@H:21]([N:24]5[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]5)[CH2:20][CH2:19]4)[N:9]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:38][C:37]2[CH:42]=[CH:43][CH:44]=[CH:45][C:36]1=2

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 613412-BenzofurancarboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178480953HCID 178480953, compound

Product 1

HCID 178476627HCID 178476627, compoundYield 11.8%

Procedure

A mixture of cis-3-(3-aminophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.107 g, 0.263 mmol, 1 equiv), glacial acetic acid (0.06 mL, 1.0 mmol, 3.8 equiv), benzo[B]furan-2-carboxaldehyde (0.1 g, 0.3 mmol, 1 equiv), sodium triacetoxyborohydride (0.212 g, 1.0 mmol, 3.8 equiv), and dichloroethane (2 mL) was stirred at ambient temperature for 4.5 h. Aqueous sodium bicarbonate was added, the organic layer was separated, and the aqueous layer was extracted with two portions of CH2Cl2 (10 mL each). The combined organic extracts were dried over MgSO4, filtered, and concentrated to afford a yellow oil which was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give cis-3-{3-[(benzo[b]furan-2-ylmethyl)amino]phenyl}-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine monoacetate salt as a white solid (0.017 g, 0.031 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.22 (1H, s), 7.51-7.58 (2H, m), 7.22-7.28 (3H, m), 6.98 (1H, s), 6.79-6.84 (2H, m), 6.59-6.62 (1H, m), 4.76-4.81 (1H, m), 4.50 (2H, d, J=5.6 Hz), 2.19-2.24 (14H, m), 2.05-2.07 (2H, m), 1.91 (3H, s), 1.60-1.75 (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 13.99 min. MS: MH+ 537.

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 combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a yellow oil which
  7. customwas purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min)
  8. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-dfa25d6033cb4c7fb6e93ef51b4b4246
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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