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

HRID 1177599Notes

Reaction equation

HRID 1177599 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-1f9deff04b88464ca779f63fdfb35fce
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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