Hydrochloric Acid → HCID 44600644, compound

HRID 1177440Notes

Reaction equation

HRID 1177440 reaction equation
[I-].C[S+](C)(C)=O.[CH3:7][C:8](C)([O-])C.[K+].[C:13]([C:21]1[N:26]=[C:25]2[S:27][C:28]([C:30]3[CH:35]=[CH:34][C:33]([CH2:36][N:37]4[CH2:40][CH:39]([C:41]([OH:43])=[O:42])[CH2:38]4)=[CH:32][C:31]=3[F:44])=[N:29][C:24]2=[CH:23][CH:22]=1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl>CC(O)(C)C.P([O-])([O-])([O-])=O.O>[F:44][C:31]1[CH:32]=[C:33]([CH2:36][N:37]2[CH2:40][CH:39]([C:41]([OH:43])=[O:42])[CH2:38]2)[CH:34]=[CH:35][C:30]=1[C:28]1[S:27][C:25]2[C:24]([N:29]=1)=[CH:23][CH:22]=[C:21]([C:13]1([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:8][CH2:7][O:20]1)[N:26]=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 67111710HCID 67111710, compound

Product 1

HCID 44600644HCID 44600644, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1061PhosphateSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of trimethylsulfoxonium iodide (230 mg, 1047 μmol) and potassium t-butoxide (1.0M in t-BuOH) (1.047 ml, 1.047 mmol) in t-BuOH (1.0 mL) was stirred at 50° C. for 30 min. 1-((4-(5-Benzoylthiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylic acid (93.7 mg, 0.209 mmol) was added in one portion, and the resulting suspension was stirred at 50° C. for 20 h. The reaction mixture was then diluted with 0.05M pH 6 phosphate buffer (2.0 mL), acidified with 1.0N HCl (750 μL), diluted with water (15 mL), and partially concentrated in vacuo. The resulting precipitate was collected by vacuum filtration, washed with water (3.0 mL), and dried in vacuo. Reverse-phase HPLC of this solid (C18, CH3CN/H2O+0.1% ammonium formate) afforded 1-((3-fluoro-4-(5-(2-phenyloxetan-2-yl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylic acid as a colorless solid. MS (ESI) m/z: Calculated: 475.1; Observed: 476.1 (M++1).

Workup

  1. stirringthe resulting suspension was stirred at 50° C. for 20 h
  2. concentrationpartially concentrated in vacuo
  3. filtrationThe resulting precipitate was collected by vacuum filtration
  4. washwashed with water (3.0 mL)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-d94bfc6fa99e475e90cffaa35ade5750
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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