Acetic Acid → HCID 178475844, compound

HRID 2056056Notes

Reaction equation

HRID 2056056 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][CH: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:4][C:3]=1[Cl:31].[CH3:32][C:33]1[O:37][C:36]([CH:38]=O)=[CH:35][CH:34]=1.[C:40]([OH:43])(=[O:42])[CH3:41].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:40]([OH:43])(=[O:42])[CH3:41].[Cl:31][C:3]1[CH:4]=[C:5]([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:6]=[CH:7][C:2]=1[NH:1][CH2:38][C:36]1[O:37][C:33]([CH3:32])=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 120975-MethylfurfuralHCID 5049666Sodium triacetoxyborohydride2×HCID 20817210HCID 20817210, compound

Product 1

HCID 178475844HCID 178475844, compoundYield 48.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 3-(4-amino-3-chlorophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.200 g, 0.00045 mol) in 1,2-dichloroethane (20 mL) was reacted with 5-methyl-2-furfural (0.052 g, 0.00048 mol), acetic acid (0.095 g, 0.00159 mol) and sodium triacetoxyborohydride (0.336 g, 0.00159 mol) at ambient temperature. An additional two equivalents of sodium triacetoxyborohydride (0.672 g, 0.00318 mol) were added in two 24 hour intervals. The solvents were removed in vacuo and the residue was partitioned between chloroform (25 mL) and saturated aqueous sodium bicarbonate (50 mL). The phases were separated and the aqueous phase was extracted with chloroform (2×25 mL). The combined organic phases were dried over magnesium sulfate, and the solvent was removed in vacuo. The residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm; 30% isocratic for five minutes, then 30%-60% acetonitrile—0.1M ammonium acetate over 15 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give trans 3-(3-chloro-4-{[(5-methyl-2-furyl)methyl]amino}phenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine acetate as a white solid (0.129 g, 0.00022 mol): 1H NMR (DMSO-d6, 400 MHz) δ 8.20 (s, 1H), 7.51 (d, 1H), 7.39 (dd, 1H), 6.93 (d, 1H), 6.20 (d, 1H), 6.14 (t, 1H), 5.98 (d, 1H), 4.55-4.66 (m, 1H), 4.38 (d, 2H), 2.23 (s, 3H), 2.18-2.61 (m, 10H), 2.14 (s, 3H), 1.91 (s, 3H), 1.87-2.09 (m, 5H), 1.37-1.53 (m, 2H); RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-95% acetonitrile—0.1M ammonium acetate over 20 min, 1 mL/min) Rt 14.48 min.; MS: MH+ 535.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue was partitioned between chloroform (25 mL) and saturated aqueous sodium bicarbonate (50 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with chloroform (2×25 mL)
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm
  8. wait30%-60% acetonitrile—0.1M ammonium acetate over 15 min
  9. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-4718f7ed7239439591ac09e6e42b26f5
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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