2-Amino-5-chloropyridine → (2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-yloxy)propanamide

HRID 1098221ノート

反応式

HRID 1098221 の反応式
C[Al](C)C.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][CH2:21][C@@H:22]([O:24][CH2:25][C@H:26]([O:31][C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][N:42]=3)[N:39]=[CH:40][C:33]=12)[C:27](OC)=[O:28])[CH3:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[Si:13]([O:20][CH2:21][C@@H:22]([O:24][CH2:25][C@H:26]([O:31][C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][N:42]=3)[N:39]=[CH:40][C:33]=12)[C:27]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([Cl:5])=[CH:11][N:10]=1)=[O:28])[CH3:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

参加物

7

反応物 4

HCID 661742-Amino-5-chloropyridineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 59279482(2S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate

生成物 1

HCID 57504541(2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-yloxy)propanamide収率 50.5%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Trimethylaluminium (2M in hexanes)(0.551 mL, 1.10 mmol) was added to 5-chloropyridin-2-amine (135 mg, 1.05 mmol) in toluene (8 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate AO2) (500 mg, 0.96 mmol) in toluene (8 mL) was added and the reaction was heated to 100° C. for 5 hours in the microwave reactor. The reaction was allowed to cool to room temperature before adding EtOAc (30 mL) and 20% sodium potassium tartrate solution (30 mL), which was stirred vigorously for 16 hours. The phases were separated and the organic layer was washed with sat. brine (15 mL), dried (MgSO4) and evaporated to give crude product (300 mg) that was used without further purification. m/z (ES+), (M+H)+=618.44; HPLC tR=23.55 min

後処理

  1. temperaturethe reaction was heated to 100° C. for 5 hours in the microwave reactor
  2. temperatureto cool to room temperature
  3. stirringwas stirred vigorously for 16 hours
  4. customThe phases were separated
  5. washthe organic layer was washed with sat. brine (15 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated

出典と根拠

ORDレコード
ord-9ef5b8660b7b44bb82939404cfecb2e3
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

読み込み中…