PyBOP → HCID 24821029, compound

HRID 1929532Notes

Reaction equation

HRID 1929532 reaction equation
C(OC([N:8]1[CH2:15][CH2:14][CH2:13][C@@:9]1([CH3:16])[C:10]([OH:12])=O)=O)(C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[F:50][C:51]1[CH:66]=[CH:65][C:54]([CH2:55][C:56]2[C:57]([CH3:64])=[C:58]([CH3:63])[C:59](=[O:62])[NH:60][N:61]=2)=[CH:53][C:52]=1[C:67]([N:69]1[CH2:74][CH2:73][NH:72][CH2:71][CH2:70]1)=[O:68]>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:50][C:51]1[CH:66]=[CH:65][C:54]([CH2:55][C:56]2[C:57]([CH3:64])=[C:58]([CH3:63])[C:59](=[O:62])[NH:60][N:61]=2)=[CH:53][C:52]=1[C:67]([N:69]1[CH2:74][CH2:73][N:72]([C:10](=[O:12])[C@:9]2([CH3:16])[CH2:13][CH2:14][CH2:15][NH:8]2)[CH2:71][CH2:70]1)=[O:68]

Participants

6

Reactant 3

HCID 2724699PyBOPHCID 11206950(2S)-1-(tert-Butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acidHCID 68839053HCID 68839053, compound

Product 1

HCID 24821029HCID 24821029, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(tert-butoxycarbonyl)-2-methylproline (1 eq), TEA (2 eq), PyBOP (1 eq) and 6-[4-fluoro-3-(piperazin-1-ylcarbonyl)benzyl]-4,5-dimethylpyridazin-3(2H)-one (II) in dry DMF (0.1 M) was heated at 60° C. with microwaves irradiation for 2 hours. The product was isolated by preparative-HPLC. After lyophilization of the pooled product fractions the residue was dissolved in 10% TFA/DCM and the solution was warmed to 45° C. for 1 h. The residue obtained after solvent evaporation was further purified by SCX cartridge. Lyophilization from water/MeCN afforded the title compound as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 12.67 (1H, s), 7.38-7.13 (3H, m), 3.96 (2H, s), 3.8-3.5 (5H, m), 3.3 (1H under water signal), 3.26-3.13 (2H, m), 2.92-2.78 (1H, m), 2.76-2.58 (1H, m), 2.34-2.15 (1H, m), 2.02 (3H, s), 2.00 (3H, s), 1.75-1.46 (3H, m), 1.26 (3H, s). MS (ES) C24H30FN5O3 requires: 455. found: 456 (M+H)+.

Workup

  1. customThe product was isolated by preparative-HPLC
  2. temperaturethe solution was warmed to 45° C. for 1 h
  3. customThe residue obtained
  4. customafter solvent evaporation
  5. customwas further purified by SCX cartridge

Sources & evidence

ORD record
ord-f16d293296d741dcaf7fd040c02b4333
Source dataset
uspto-grants-2012_05
Patent number
US08188084B2

Reaction notes

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