Diisopropylethylamine → 9H-9-fluorenylmethyl N-{2-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-1,1-dimethyl-2-oxoethyl}-N-methylcarbamate

HRID 897901ノート

反応式

HRID 897901 の反応式
Cl.Cl.[I:3][C:4]1[C:12]2[C:7](=[N:8][CH:9]=[N:10][C:11]=2[NH2:13])[N:6]([CH:14]2[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]2)[N:5]=1.[CH:20]1[C:32]2[CH:31]([CH2:33][O:34][C:35]([N:37]([CH3:44])[C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40])=[O:36])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2N=CC=CC=2N=N1>ClCCl>[NH2:13][C:11]1[N:10]=[CH:9][N:8]=[C:7]2[N:6]([CH:14]3[CH2:19][CH2:18][CH2:17][N:16]([C:39](=[O:40])[C:38]([N:37]([CH3:44])[C:35](=[O:36])[O:34][CH2:33][CH:31]4[C:30]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[C:24]5[C:32]4=[CH:20][CH:21]=[CH:22][CH:23]=5)([CH3:43])[CH3:42])[CH2:15]3)[N:5]=[C:4]([I:3])[C:12]=12

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 4147680Fmoc-N-Me-Aib-OH2 回HCID 223471203-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride

生成物 1

HCID 223473249H-9-fluorenylmethyl N-{2-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-1,1-dimethyl-2-oxoethyl}-N-methylcarbamate収率 11.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 3-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (0.17 g, 0.00042 mol), 2-[[(9H-9-fluorenylmethoxy)carbonyl]-(methyl)amino]-2-methylpropanoic acid (0.175 g, 0.00052 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.1 g, 0.00052 mol), N,N-diisopropylethylamine (0.23 g, 0.0018 mol) and 1-hydroxy-7-azabenzotriazole (0.057 g, 0.00042 mol) in anhydrous dichloromethane (7 mL) was stirred for 18 hours at room temperature. Additional 2-[[(9H-9-fluorenylmethoxy)carbonyl](methyl)amino]-2-methylpropanoic acid (0.044 g, 0.00013 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.025 g, 0.00013 mol) were added to the reaction and stirred for 16 hours. The solvent was removed under reduced pressure. The residue was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic solvent was removed under reduced pressure, and the residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 20 min with 0.1 M ammonium acetate, 21 mL/min) to yield 9H-9-fluorenylmethyl N-{2-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-1,1-dimethyl-2-oxoethyl}-N-methylcarbamate (0.030 g, 0.00005 mol).

後処理

  1. stirringstirred for 16 hours
  2. customThe solvent was removed under reduced pressure
  3. customThe residue was partitioned between brine and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. customthe combined organic solvent was removed under reduced pressure
  6. customthe residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 20 min with 0.1 M ammonium acetate, 21 mL/min)

出典と根拠

ORDレコード
ord-e927fdb9b120422d9ace040519e46d1e
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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