Triethylamine → 5-(4-Isopropylsulfonylphenyl)-3-[5-[4-[1-(methylamino)ethyl]phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-amine

HRID 2204879Notes

Reaction equation

HRID 2204879 reaction equation
[NH2:1][C:2]1[C:3]([C:20]2[O:24][C:23]([C:25]3[CH:30]=[CH:29][C:28]([C:31](=O)[CH3:32])=[CH:27][CH:26]=3)=[N:22][N:21]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.Cl.CN.[CH2:37]([N:39](CC)CC)C.[BH4-].[Na+]>C(O)C.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[CH:17]([S:14]([C:11]1[CH:10]=[CH:9][C:8]([C:5]2[N:4]=[C:3]([C:20]3[O:24][C:23]([C:25]4[CH:26]=[CH:27][C:28]([CH:31]([NH:39][CH3:37])[CH3:32])=[CH:29][CH:30]=4)=[N:22][N:21]=3)[C:2]([NH2:1])=[N:7][CH:6]=2)=[CH:13][CH:12]=1)(=[O:16])=[O:15])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 6364545Methylamine hydrochlorideHCID 594716731-[4-[5-[3-Amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]ethanone

Product 1

HCID 594718625-(4-Isopropylsulfonylphenyl)-3-[5-[4-[1-(methylamino)ethyl]phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-amineYield 22%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolvent

Procedure

A mixture of 1-[4-[5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]ethanone (130 mg, 0.2805 mmol), methylamine hydrochloride (37.88 mg, 0.5610 mmol), Ti(OiPr)4 (159.4 mg, 165.5 μL, 0.5610 mmol) and triethylamine (56.77 mg, 78.20 μL, 0.5610 mmol) was stirred at room temperature in ethanol (2 mL) under nitrogen overnight. The reaction mixture was treated with sodium borohydride (15.92 mg, 16.85 μL, 0.4208 mmol) and stirred at room temperature over weekend and then was quenched with aqueous ammonia (1 mL conc in 4 mL water). The mixture was extracted with dichloromethane and the organic extracts dried over MgSO4 and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The product fractions were passed through a bicarbonate cartridge and concentrated in vacuo. The solid was triturated with acetonitrile to give the product as a pale yellow solid (27.0 mg, 22%); 1H NMR (400 MHz, DMSO) d 1.20 (d, 6H), 1.28 (d, 3H), 4.48 (m, 1H), 3.69 (q, 1H), 7.72 (d, 2H), 7.97 (d, 2H), 7.98 (v br s, 2H), 8.12 (d, 2H) and 9.07 (s, 1H) ppm; MS (ES+) 479.3

Workup

  1. customwas quenched with aqueous ammonia (1 mL conc in 4 mL water)
  2. extractionThe mixture was extracted with dichloromethane
  3. dry with materialthe organic extracts dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. concentrationconcentrated in vacuo
  7. customThe solid was triturated with acetonitrile

Sources & evidence

ORD record
ord-93bd3f296d97475ba4770e10d8d45c50
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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