Citric Acid → Azd8055

HRID 218348ノート

反応式

HRID 218348 の反応式
[OH-].[K+].C([O:9][CH2:10][C:11]1[CH:16]=[C:15]([C:17]2[CH:18]=[CH:19][C:20]3[C:25]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]4[CH3:32])=[N:24][C:23]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][C@@H:34]4[CH3:39])=[N:22][C:21]=3[N:40]=2)[CH:14]=[CH:13][C:12]=1[O:41][CH3:42])(=O)C(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(Cl)Cl>C1COCC1.CO>[CH3:39][C@H:34]1[CH2:35][O:36][CH2:37][CH2:38][N:33]1[C:23]1[N:24]=[C:25]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]2[CH3:32])[C:20]2[CH:19]=[CH:18][C:17]([C:15]3[CH:14]=[CH:13][C:12]([O:41][CH3:42])=[C:11]([CH2:10][OH:9])[CH:16]=3)=[N:40][C:21]=2[N:22]=1

参加物

7

反応物 4

HCID 311Citric AcidHCID 6344DichloromethaneHCID 14797Potassium HydroxideHCID 58015470HCID 58015470、化合物

生成物 1

HCID 25262965Azd8055収率 95.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Potassium hydroxide solution (1.7 mL, 3.10 mmol) was added to a solution of 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzyl pivalate (172 mg, 0.30 mmol) in THF (6.9 mL) and methanol (1.7 mL) at RT under an atmosphere of nitrogen. After 240 minutes, HPLC analysis showed complete disappearance of the starting material. The reaction was maintained at RT overnight (for convenience) and aqueous citric acid (20% w/v, 2 mL) was added followed by methylene chloride (15 mL). The upper aqueous layer was extracted with two further extractions of methylene chloride (2×15 mL) and the organic layers combined. Evaporation of the methylene chloride afforded (5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol (6) as a yellow solid (133 mg).

後処理

  1. additionwas added
  2. extractionThe upper aqueous layer was extracted with two further extractions of methylene chloride (2×15 mL)
  3. customEvaporation of the methylene chloride

出典と根拠

ORDレコード
ord-1e8fd2605e1a40998b3229de0c17020b
出典データセット
uspto-grants-2012_06
特許番号
US08198441B2

反応ノート

読み込み中…