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

HRID 1177599노트

반응식

HRID 1177599 반응식
[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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1f9deff04b88464ca779f63fdfb35fce
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842685B2

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