3-Chloro-4-fluoroaniline → 2-Bromo-6-(4-chloro-3-fluoro-phenyl)-5-[5-chloro-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-pyridin-3-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

HRID 2204347Notes

Reaction equation

HRID 2204347 reaction equation
[NH2:1][C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C[O:20][C:21]([C:23]1[CH:27]=[C:26]([Br:28])[N:25]([CH:29]([CH3:31])[CH3:30])[C:24]=1[CH:32]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)O)=O.ClC1C=C(C=CC=1[F:49])N.ClC(N(C)C)=C(C)C>C(Cl)Cl.CO.CCN(CC)CC>[Br:28][C:26]1[N:25]([CH:29]([CH3:31])[CH3:30])[C:24]2[CH:32]([C:34]3[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([F:49])[CH:35]=3)[N:1]([C:2]3[C:3](=[O:18])[N:4]([CH2:9][C:10]4[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=4)[CH:5]=[C:6]([Cl:8])[CH:7]=3)[C:21](=[O:20])[C:23]=2[CH:27]=1

Participants

7

Reactant 4

HCID 97083-Chloro-4-fluoroanilineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 867031015-bromo-2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl esterHCID 867031523-amino-5-chloro-1-(4-methoxy-benzyl)-1H-pyridin-2-one

Product 1

HCID 867031512-Bromo-6-(4-chloro-3-fluoro-phenyl)-5-[5-chloro-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-pyridin-3-yl]-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

The title compound was prepared in analogy to the procedure described for Intermediate D but in the step corresponding to Step D2,5-bromo-2-[(4-chloro-3-fluoro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (Step AZ1) and 3-amino-5-chloro-1-(4-methoxy-benzyl)-1H-pyridin-2-one (Step AH1) were used instead of 5-bromo-2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester and 3-chloro-4-fluoroaniline respectively. Moreover, in this step, the procedures described for Steps H3 and H2 using 1-chloro-N,N,2-trimethylpropenylamine and Et3N were used. The title compound (containing some of the corresponding 2-chloro analog) was obtained as a yellow-brown solid. tR: 7.83 min (HPLC 2); ESI-MS: tR=1.36 min, [M+H]+ 618/620/622 (LC-MS 1); TLC: Rf=0.50 (98:2 CH2Cl2/MeOH).

Workup

  1. customThe title compound was prepared in analogy to the procedure
  2. customwas obtained as a yellow-brown solid

Sources & evidence

ORD record
ord-9131d8773a464f92b4f74cd334eadf51
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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