Sodium Hydroxide → 4-(((3S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid

HRID 877794ノート

反応式

HRID 877794 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([NH:14][C:15]2[C:16]3[N:17]([CH:24]=[C:25]([C:27]([O:29]CC)=[O:28])[CH:26]=3)[N:18]=[CH:19][C:20]=2[C:21](=[O:23])[NH2:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([NH:14][C:15]2[C:16]3[N:17]([CH:24]=[C:25]([C:27]([OH:29])=[O:28])[CH:26]=3)[N:18]=[CH:19][C:20]=2[C:21](=[O:23])[NH2:22])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

4

反応物 2

HCID 14798Sodium Hydroxide2 回HCID 68291296ethyl 4-(((3S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

生成物 1

HCID 682909544-(((3S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid収率 100%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of ethyl 4-(((3S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (585 mg, 1.356 mmol) and NaOH, 1N (3.39 mL, 3.39 mmol) in THF (14 mL) was stirred at rt for 4 days. At the end of each day, additional NaOH, 1N (3.39 mL, 3.39 mmol) was added, for a total of three additions. The reaction mixture was partitioned between ˜70 ml of EtOAc and 50 ml of water. While stirring the biphasic mixture, the pH was adjusted to ˜2 with saturated KHSO4 solution. The layers were separated and the aqueous layer was extracted with DCM (50 ml). A precipitant began to form in the combined organic layer. The solid was very fine and the suspension was dried over Na2SO4. The supernate was decanted off and the sodium sulfate was thoroughly rinsed with hot EtOAc and hot MeOH. The decanted supernates were concentrated to afford 4-(((3S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid (545 mg, 1.351 mmol, 100% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 12.51 (br. s., 1H), 11.23 (br. s., 1H), 8.32 (s, 1H), 8.07 (d, J=1.3 Hz, 1H), 7.19 (d, J=1.3 Hz, 1H), 4.76 (d, J=15.0 Hz, 1H), 3.83-3.51 (m, 2H), 3.40-3.34 (m, 1H), 3.09-2.87 (m, 1H), 2.58 (d, J=7.5 Hz, 1H), 1.37 (d, J=13.2 Hz, 9H), 1.13-0.86 (m, 3H). MS (ES+) m/z: 304.2 (M+H-Boc); LC retention time: 2.533 min (analytical HPLC Method O).

後処理

  1. customThe reaction mixture was partitioned between ˜70 ml of EtOAc and 50 ml of water
  2. stirringWhile stirring the biphasic mixture
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (50 ml)
  5. customto form in the combined organic layer
  6. dry with materialthe suspension was dried over Na2SO4
  7. customThe supernate was decanted off
  8. washthe sodium sulfate was thoroughly rinsed with hot EtOAc and hot MeOH
  9. concentrationThe decanted supernates were concentrated

出典と根拠

ORDレコード
ord-5400019e93674ba4b0ee778d1aeaa3a5
出典データセット
uspto-grants-2015_03
特許番号
US08987268B2

反応ノート

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