Sodium Hydroxide → HCID 54579596, compound

HRID 1942763Notes

Reaction equation

HRID 1942763 reaction equation
[CH2:1]([C:3]1[C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])[CH2:20][CH2:19]1)[CH3:2].Br[C:32]1[N:36]=[C:35]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH:44]([CH3:46])[CH3:45])=[C:39]([Cl:47])[CH:38]=2)[S:34][N:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(O)=O.O.C(O)(C)C>[Cl:47][C:39]1[CH:38]=[C:37]([C:35]2[S:34][N:33]=[C:32]([C:8]3[C:3]([CH2:1][CH3:2])=[C:4]([CH:18]4[CH2:19][CH2:20][N:21]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])[CH2:22][CH2:23]4)[CH:5]=[CH:6][CH:7]=3)[N:36]=2)[CH:42]=[CH:41][C:40]=1[O:43][CH:44]([CH3:45])[CH3:46]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 58494048HCID 58494048, compoundHCID 584940863-Bromo-5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazole

Product 1

HCID 54579596HCID 54579596, compoundYield 16.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl 3-{4-[2-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-piperidinyl}propanoate (D123) (200 mg, 0.481 mmol), 3-bromo-5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazole (D43) (161 mg, 0.481 mmol) and Pd(Ph3P)4 (55.6 mg, 0.048 mmol) was added tripotassium phosphate (307 mg, 1.444 mmol) under nitrogen. The solution was sealed for Biotage microwave irradiation at 120° C. for 20 min. To the resulted solution, Isopropanol (10 mL) and water (2 mL) and then sodium hydroxide (0.5 mL, 3.05 mmol) was added. This solution was stirred at 50° C. for 2 hr. The solution was neutralized with AcOH, dried, dissolved in DMF and purified by Mass Directed AutoPrep to afford 3-{4-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]-1-piperidinyl}propanoic acid (E100) (40 mg).

Workup

  1. customThe solution was sealed for Biotage microwave irradiation at 120° C. for 20 min
  2. customdried
  3. dissolutiondissolved in DMF
  4. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-aefc3f8c537f49879a324c475200a646
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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