Hydrochloric Acid → 2-[({5-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]ethanol

HRID 38880

Reaction equation

HRID 38880 reaction equation
Cl[CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:16]=[C:15]([C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH:14]=[C:13]3[C:9]=2[CH:10]=[N:11][N:12]3S(C2C=CC=CC=2)(=O)=O)=[N:5][N:4]=1.[NH2:35][CH2:36][CH2:37][OH:38].[OH-].[Na+].Cl>C(#N)C.CS(C)=O.CO.C(O)(C)C>[NH:21]1[C:22]2[C:18](=[C:17]([C:15]3[CH:14]=[C:13]4[C:9]([CH:10]=[N:11][NH:12]4)=[C:8]([C:6]4[O:7][C:3]([CH2:2][NH:35][CH2:36][CH2:37][OH:38])=[N:4][N:5]=4)[CH:16]=3)[CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:20]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 700EthanolamineHCID 14798Sodium HydroxideHCID 667769544-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 666916212-[({5-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]ethanolYield 14.5%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent2×HCID 22036561Dimethyl sulfoxide methanolSolvent

Conditions

Temperature
100 °C

Procedure

4-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole (100 mg, 0.184 mmol) in acetonitrile (2 ml) was treated with 2-aminoethanol (0.055 ml, 0.918 mmol) and heated in a microwave at 100° C. for 30 mins. The acetonitrile supernatant was pipetted off, and the solid washed with further acetonitrile (5 ml). The solid was dissolved in methanol and DMSO (1:1, 3 ml) and loaded onto a 2 g SCX cartridge. Methanol was eluted, then 2M ammonia in ethanol. Basic fractions were blown to dryness to give a brown solid. The fully-protected intermediate was treated with isopropanol (1.000 ml) followed by 2M aqueous sodium hydroxide (1.001 ml, 2.002 mmol) and stirred for 20 h at 20° C. The solution was neutralised by addition of 2M hydrochloric acid, then blown to dryness to give a brown solid. This was transferred into a small vial, and treated with DMSO/MeOH (1:1, 1 ml) then filtered and purified on MDAP (Method E). The appropriate fraction was blown to dryness to give the title compound as a beige solid (10 mg).

Workup

  1. washthe solid washed with further acetonitrile (5 ml)
  2. dissolutionThe solid was dissolved in methanol
  3. washMethanol was eluted
  4. customto give a brown solid
  5. customto give a brown solid
  6. filtrationthen filtered
  7. custompurified on MDAP (Method E)

Sources & evidence

ORD record
ord-fe483585a71f48a0b98f2903abcf0daa
Source dataset
uspto-grants-2013_09
Patent number
US08524751B2

Linked notes

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