Hydrochloric Acid → HCID 67003539, compound

HRID 2362702Notes

Reaction equation

HRID 2362702 reaction equation
[F:1][C:2]1[C:3]([C:21]2[S:25][C:24]([C:26]3([O:37]COC)[CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]3)=[N:23][CH:22]=2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1.CO.Cl>[Cl-].[Na+].O.C(OCC)(=O)C>[F:1][C:2]1[C:3]([C:21]2[S:25][C:24]([C:26]3([OH:37])[CH2:29][NH:28][CH2:27]3)=[N:23][CH:22]=2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 67003692HCID 67003692, compound

Product 1

HCID 67003539HCID 67003539, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A flask was charged with tert-butyl 3-(5-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)-3-(methoxymethoxy)azetidine-1-carboxylate (Example 54B) (500 mg, 0.849 mmol), methanol (6.5 mL) and aqueous 2 molar HCl solution (2.58 mL, 8.49 mmol). The reaction mixture was heated to 60° C. for 5 hours, then 35° C. overnight. The reaction mixture was cooled to room temperature and diluted with saturated aqueous brine solution and ethyl acetate. The layers were separated, and the aqueous layer extracted with ethyl acetate (3×20 mL). The organic layers were combined and concentrated. The remaining solid was triturated with water (pH approximately 10). The solids were collected by vacuum filtration, washed with water, and dried at low temperature in a vacuum oven to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 8.50 (d, 1H), 8.40 (s, 1H), 8.10 (d, 1H), 8.01 (d, 2H), 7.44 (d, 2H), 7.14 (d, 1H), 7.06 (s, 1H), 3.96 (d, 2H), 3.71 (d, 2H), 2.35 (s, 3H); MS APCI(+) m/z 445.22 (M+H)+.

Workup

  1. custom35° C. overnight
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with ethyl acetate (3×20 mL)
  5. concentrationconcentrated
  6. customThe remaining solid was triturated with water (pH approximately 10)
  7. filtrationThe solids were collected by vacuum filtration
  8. washwashed with water
  9. customdried at low temperature in a vacuum oven

Sources & evidence

ORD record
ord-77bae4319c854c2cae3507d41596b947
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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