1-Hydroxybenzotriazole → N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)-propanamide

HRID 1842925Notes

Reaction equation

HRID 1842925 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]([CH3:17])[C:14]([OH:16])=O)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][CH2:11][OH:12].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[C:59]([C:63]1[CH:67]=[C:66]([CH2:68][NH2:69])[N:65]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([Cl:76])[CH:71]=2)[N:64]=1)([CH3:62])([CH3:61])[CH3:60]>C1COCC1.CN(C=O)C>[C:59]([C:63]1[CH:67]=[C:66]([CH2:68][NH:69][C:14](=[O:16])[CH:13]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][O:9][CH2:10][CH2:11][OH:12])=[C:2]([F:1])[CH:3]=2)[CH3:17])[N:65]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([Cl:76])[CH:71]=2)[N:64]=1)([CH3:62])([CH3:60])[CH3:61]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58093530(3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methanamineHCID 708158662-(3-Fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid

Product 1

HCID 70816296N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)-propanamideYield 87%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a stirred THF/DMF (2.0 mL/0.1 mL) solution of 2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)propanoic acid (synthesis described for example A118) (60.0 mg, 0.25 mmol, 1.0 eq) DIPEA (0.169 mL, 0.13 mmol, 4.0 eq), TBTU (81 mg, 0.25 mmol, leg) and HOBt (33 mg, 0.25 mmol, leg) were sequentially added at RT and the mixture stirred for 15 min. (3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methanamine (65 mg, 0.25 mmol, 1 eq) was then added and the mixture stirred for 36 h. After completion of the reaction the solvent was evaporated. The crude product was purified by CC using EtOAc/cyclohexane (1:1) to get N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)-propanamide (106 mg; 87%).

Workup

  1. customwere sequentially added at RT
  2. additionwas then added
  3. customAfter completion of the reaction the solvent
  4. customwas evaporated
  5. customThe crude product was purified by CC

Sources & evidence

ORD record
ord-fee535830a674ee58e295bd7efde4150
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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