Potassium Carbonate → (4-{3-[3-(3-tert-butoxycarbonylamino-1-phenyl-propylamino)-phenyl]-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester

HRID 1809765ノート

反応式

HRID 1809765 の反応式
[C:1]([O:5][C:6](=[O:50])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([C:31]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:51]([O:55][C:56](=[O:68])[NH:57][CH2:58][CH2:59][CH:60]([NH2:67])[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)([CH3:54])([CH3:53])[CH3:52].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([O:5][C:6](=[O:50])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([C:31]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:67][CH:60]([C:61]5[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=5)[CH2:59][CH2:58][NH:57][C:56]([O:55][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:68])[CH:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57826906Tert-butyl 3-amino-3-phenylpropylcarbamateHCID 68109074HCID 68109074、化合物

生成物 1

HCID 68108109(4-{3-[3-(3-tert-butoxycarbonylamino-1-phenyl-propylamino)-phenyl]-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A sealed tube was charged with {4-[3-(3-bromo-phenyl)-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 43 supra) (500 mg, 0.686 mmol), (3-amino-3-phenyl-propyl)-carbamic acid tert-butyl ester (from Example 2 supra) (258 mg, 1.03 mmol), DavePhos (54 mg, 0.137 mmol), K2CO3 (142 mg, 1.03 mmol), Pd2(dba)3 (31 mg, 0.0343 mmol) and 1,4-dioxane (14 mL). This mixture was stirred at 120° C. for 15 hours under an atmosphere of N2. The mixture was cooled and filtered; the filtrate was evaporated under reduced pressure to give the crude product. It was purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH, 200:1 to 50:1), then by prep-HPLC to give (4-{3-[3-(3-tert-butoxycarbonylamino-1-phenyl-propylamino)-phenyl]-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester. (Yield 63 mg, 10.2%).

後処理

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. customthe filtrate was evaporated under reduced pressure
  4. customto give the crude product
  5. customIt was purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH, 200:1 to 50:1)

出典と根拠

ORDレコード
ord-1c00e02701bc4ed599d6a6a80497e675
出典データセット
uspto-grants-2013_01
特許番号
US08362023B2

反応ノート

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