Acetic Acid → benzyl 4-[4-amino-3-(3-methoxy-4-{[(5-methyl-2-furyl)methyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate

HRID 432518

反応式

HRID 432518 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])[CH2:22][CH2:21]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12.[CH3:36][C:37]1[O:43][C:40]([CH:41]=O)=[CH:39][CH:38]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[O:27])[CH2:22][CH2:21]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][CH2:41][C:40]4[O:43][C:37]([CH3:36])=[CH:38][CH:39]=4)=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12

参加物

6

反応物 4

HCID 176Acetic AcidHCID 120975-MethylfurfuralHCID 5049666Sodium triacetoxyborohydrideHCID 22346984benzyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate

生成物 1

HCID 22346718benzyl 4-[4-amino-3-(3-methoxy-4-{[(5-methyl-2-furyl)methyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate収率 73%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

A mixture of benzyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (3.0 g, 0.0063 mol), 5-methylfurfural (0.77 g, 0.007 mol), and acetic acid (1.15 g, 0.019 mol) in dichloroethane (100 mL) was stirred at room temperature under an atmosphere of nitrogen for 1.5 hrs. Sodium triacetoxyborohydride (4.1 g, 0.0195 mol) was added to the mixture and the mixture was stirred at ambient temperature under an atmosphere of nitrogen for 18 hours. The reaction was quenched with an aqueous 5N solution of sodium hydroxide. The solvents were removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (3×200 mL), and the combined organic layer was washed with water and brine, and dried over magnesium sulfate. The solvents were removed under reduced pressure. The residue was purified by flash chromatography on silica gel using 2%-5% methanol/dichloromethane as mobile phase to yield benzyl 4-[4-amino-3-(3-methoxy-4-{[(5-methyl-2-furyl)methyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (2.63 g, 0.0046 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 11.59 min. MS: MH+ 568.

後処理

  1. stirringthe mixture was stirred at ambient temperature under an atmosphere of nitrogen for 18 hours
  2. customThe reaction was quenched with an aqueous 5N solution of sodium hydroxide
  3. customThe solvents were removed under reduced pressure
  4. customthe residue was partitioned between water and dichloromethane
  5. extractionThe aqueous layer was extracted with dichloromethane (3×200 mL)
  6. washthe combined organic layer was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvents were removed under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel using 2%-5% methanol/dichloromethane as mobile phase

出典と根拠

ORDレコード
ord-62f5bde84aca4fcc99ad56b6150ebd1e
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

関連ノート

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