Sodium Bicarbonate → HCID 58042295, compound

HRID 1619652Notes

Reaction equation

HRID 1619652 reaction equation
[Cl:1][C:2]1[C:3]([O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=3)=[CH:32][C:31]=2[C:46](=O)/[CH:47]=[CH:48]/N(C)C)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.[NH:53]([CH:55]1[CH2:58][N:57]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:56]1)[NH2:54].C(=O)([O-])O.[Na+]>C(O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[C:5]([F:28])=[CH:4][C:3]=1[O:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:43])[F:44])=[CH:38][CH:37]=2)=[CH:32][C:31]=1[C:46]1[N:53]([CH:55]2[CH2:56][N:57]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:58]2)[N:54]=[CH:48][CH:47]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 58042244HCID 58042244, compoundHCID 58042291Tert-butyl 3-hydrazinylazetidine-1-carboxylate

Product 1

HCID 58042295HCID 58042295, compoundYield 280.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Conditions

Temperature
70 °C

Procedure

5-Chloro-N-(2,4-dimethoxybenzyl)-4-({3-[(2E)-3-(dimethylamino)prop-2-enoyl]-4′-(trifluoromethyl)biphenyl-4-yl}oxy)-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 39, 504 mg, 0.648 mmol) in ethanol (10 mL) was slowly added a solution of tert-butyl 3-hydrazinoazetidine-1-carboxylate (Preparation 36, 536 mg, 2.86 mmol) in ethanol (10 mL) and acetic acid (0.23 mL) at 0° C. under nitrogen. The reaction was heated to 70° C. for 3 hours and then cooled to room temperature. The reaction mixture was neutralised to pH 7 with saturated aqueous sodium hydrogen carbonate solution (2 mL) and concentrated in vacuo to afford a yellow oil. The oil was partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (2×100 mL) dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil (1.64 g). The oil was partially purified by silica gel column chromatography (0%-10% methanol in dichloromethane) to afford the title compound as a brown oil (419 mg) of 39% purity via LCMS. The compound was used without further purification in the next step.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customto afford a yellow oil
  4. customThe oil was partitioned between water (100 mL) and ethyl acetate (100 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic layers were washed with brine (2×100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c23700a99c0c4f2cb79b4693c1c774db
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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