Sodium Carbonate → (2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500729ノート

反応式

HRID 500729 の反応式
[CH3:1][C:2]1[NH:19][C:5]2=[N:6][CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=[C:4]2[CH:3]=1.I[C:21]1[C:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH2:33][C@@H:34]([OH:36])[CH3:35])[N:27]=2)=[CH:24][N:23]([CH:37]([CH3:39])[CH3:38])[N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:37]([N:23]1[CH:24]=[C:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH2:33][C@@H:34]([OH:36])[CH3:35])[N:27]=2)[C:21]([C:8]2[CH:9]=[C:4]3[CH:3]=[C:2]([CH3:1])[NH:19][C:5]3=[N:6][CH:7]=2)=[N:22]1)([CH3:39])[CH3:38]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 533986352-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrrolo[2,3-B]pyridineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

生成物 1

HCID 25181762(2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol収率 18.6%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 21863594Toluene ethanol溶媒

反応条件

温度
80 °C

実験手順

To a suspension of 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (B-7-7) (1.8 g, 2.3 mmol in the theory) and (2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-1-3) (0.45 g, 1.2 mmol) in toluene/EtOH (3:1, 50 mL) was added aq. Na2CO3 (1.7 mL, 2 M). The mixture was degassed under N2 for 2 minutes, Pd(PPh3)4 (0.05 g, 0.042 mmol) was added into the mixture and degassed again. The mixture was stirred at 80° C. for 30 hours. TLC (CH2Cl2: MeOH=20:1) showed that the reaction was complete. Water (50 mL) and EtOAc (50 mL×3) were added into the mixture. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated to give crude product which was purified via prep. HPLC to afford (2S)-1-(4-(1-isopropyl-3-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-7) (0.169 g, 18.6%) as a white solid.

後処理

  1. customThe mixture was degassed under N2 for 2 minutes
  2. customdegassed again
  3. additionWater (50 mL) and EtOAc (50 mL×3) were added into the mixture
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto give crude product which
  8. customwas purified via prep

出典と根拠

ORDレコード
ord-715c54ba036c463b834c825b4bac5076
出典データセット
uspto-grants-2010_08
特許番号
US07772246B2

反応ノート

読み込み中…