2-Propanol, 2-methyl-, lithium salt (1:1) → HCID 86719973, compound

HRID 1617333Notes

Reaction equation

HRID 1617333 reaction equation
[CH3:1][O:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH:13]([C:15]3[NH:19][N:18]=[CH:17][CH:16]=3)[CH3:14])=[CH:12][C:7]=2[S:6][C:5]1=[O:20].CC(C)([O-])C.[Li+].F[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][O:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][O:39]2)=[CH:30][N:29]=1>CN(C)C=O.C1COCC1>[CH3:1][O:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH:13]([C:15]3[CH:16]=[CH:17][N:18]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][O:37][CH:38]5[CH2:43][CH2:42][CH2:41][CH2:40][O:39]5)=[CH:30][N:29]=4)[N:19]=3)[CH3:14])=[CH:12][C:7]=2[S:6][C:5]1=[O:20]

Participants

6

Reactant 3

HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86719971HCID 86719971, compoundHCID 86719972HCID 86719972, compound

Product 1

HCID 86719973HCID 86719973, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 3-(methoxymethyl)-6-[1-(1H-pyrazol-5-yl)ethyl]-3H-1,3-benzothiazol-2-one (7.7 g, 26.6 mmoles) in dimethylformamide (0.2 M; 133 mL). Add lithium t-butoxide ((1.5 Eq of a 1.00 molar solution in THF), 39.9 mmoles; 39.9 mL)) and stir 15 min. Add 2-fluoro-5-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine (2.00 Eq; 53.2 mmoles; 12.8 g). Heat the reaction in an oil bath to 140° C. and purge with N2 to remove THF. Heat the mixture at reflux for 5 hr. Cool the mixture to room temperature and quench with saturated ammonium chloride. Extract into EtOAc (2×200 mL), wash with water (2×100 mL), followed by brine (200 mL). Dry over sodium sulfate, filter and concentrate. Purify by HPLC (silica) eluting with 40% EtOAc/hexanes to give 3-(methoxymethyl)-6-{1-[1-(5-{2-(tetrahydro-2H-pyran-2-yloxy)ethoxy}pyridine-2-yl)-1H-pyrazol-3-yl]ethyl}-3H-1,3-benzothiazol-2-one as a pale yellow oil (10 g; 19.6 mmoles, 74% yield). LCMS (low) rt=2.6, M+1=511.

Workup

  1. temperatureHeat
  2. customthe reaction in an oil bath to 140° C.
  3. custompurge with N2
  4. customto remove THF
  5. temperatureHeat the mixture
  6. temperatureat reflux for 5 hr
  7. customquench with saturated ammonium chloride
  8. extractionExtract into EtOAc (2×200 mL)
  9. washwash with water (2×100 mL)
  10. dry with materialDry over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate
  13. customPurify by HPLC (silica)
  14. washeluting with 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-18766432ff1c48f19980e129e64e0762
Source dataset
uspto-grants-2014_07
Patent number
US08765960B2

Reaction notes

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