Ammonium Chloride → 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide
Reaction equation
[NH2:1][C:2]1([CH2:6][OH:7])[CH2:5][CH2:4][CH2:3]1.[CH3:8]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH4+].[Cl-].[C:32]([C:34]1[CH:35]=[N:36][C:37]2[C:42]([CH:43]=1)=[CH:41][C:40]([O:44][C:45](C)([SH:49])[C:46](O)=[O:47])=[CH:39][CH:38]=2)#[CH:33]>CC#N.CCN(CC)CC>[C:32]([C:34]1[CH:35]=[N:36][C:37]2[C:42]([CH:43]=1)=[CH:41][C:40]([O:44][CH:45]([S:49][CH3:8])[C:46]([NH:1][C:2]1([CH2:6][OH:7])[CH2:5][CH2:4][CH2:3]1)=[O:47])=[CH:39][CH:38]=2)#[CH:33]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a mixture containing (1-amino-cyclobutyl)-methanol (preparation described in JP 08134044) (860 mg), aza-HOBT (600 mg), TBTU (1.41 g) and Et3N (1 ml) in CH3CN (30 ml), (3-ethynyl-quinolin-6-yloxy)-methyl sulfanyl-acetic acid dissolved in Et3N (1 ml) and CH3CN (30 ml) was added over 1 hr, at room temperature, under nitrogen atmosphere. The resulting brown suspension was stirred overnight at room temperature then poured into aq NH4Cl solution and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulphate anhydrous, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 1/3) to give 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide (1.09 g) as slightly yellow solid.
Workup
- extractionextracted with ethyl acetate
- washThe combined organic layers were washed with water, brine
- dry with materialdried over sodium sulphate anhydrous
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe crude residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 1/3)
Sources & evidence
- ORD record
- ord-b5b2c18d0d9542fd91d48f0de30f6f26
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415272B2
Reaction notes
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