Hydrochloric Acid → 4-(5-(1-(3,3-Difluorocyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-3-fluorobenzaldehyde

HRID 1177599ノート

反応式

HRID 1177599 の反応式
[O:1]1CCCO[CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]2([CH:25]4[CH2:28][C:27]([F:30])([F:29])[CH2:26]4)[CH2:24][CH2:23]2)[N:16]=3)=[C:9]([F:31])[CH:8]=1.Cl.[OH-].[Na+]>C1COCC1>[F:30][C:27]1([F:29])[CH2:26][CH:25]([C:22]2([C:17]3[N:16]=[C:15]4[S:14][C:13]([C:10]5[CH:11]=[CH:12][C:7]([CH:2]=[O:1])=[CH:8][C:9]=5[F:31])=[N:21][C:20]4=[CH:19][CH:18]=3)[CH2:23][CH2:24]2)[CH2:28]1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 671115762-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridine

生成物 1

HCID 866387274-(5-(1-(3,3-Difluorocyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-3-fluorobenzaldehyde

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

A mixture of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridine (151.5 mg, 0.339 mmol) and hydrochloric acid (5.0N, aq.) (3.0 mL, 15.00 mmol) in THF (6.7 mL) was stirred at 65° C. for 3 h. Ther reaction mixture was then cooled on an ice bath, and NaOH (5.0N, aq.; 3.0 mL) was added. THF was removed in vacuo, and the resulting mixture was partitioned between EtOAc (100 mL) and water (30 mL). The organic layer was separated, sequentially washed with water (30 mL) and brine (20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-60% EtOAc/hexanes) furnished 4-(5-(1-(3,3-difluoro-cyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-3-fluorobenzaldehyde as a light-yellow solid. MS (ESI) m/z: Calculated: 388.1; Observed: 389.0 (M++1).

後処理

  1. temperatureTher reaction mixture was then cooled on an ice bath
  2. customTHF was removed in vacuo
  3. customthe resulting mixture was partitioned between EtOAc (100 mL) and water (30 mL)
  4. customThe organic layer was separated
  5. washsequentially washed with water (30 mL) and brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0-60% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-1f9deff04b88464ca779f63fdfb35fce
出典データセット
uspto-grants-2010_11
特許番号
US07842685B2

反応ノート

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