Dichloromethane → HCID 72206457, compound

HRID 2204362Notes

Reaction equation

HRID 2204362 reaction equation
Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[N:11]([C:14]3[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=3[CH3:21])[C:12](=[O:13])[C:4]=2[CH:3]=1.[CH3:29][O:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=[C:33]([NH2:46])[N:32]=1.C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1.O>[NH2:46][C:33]1[N:32]=[C:31]([O:30][CH3:29])[C:36]([C:2]2[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]3[CH:10]([C:22]4[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=4)[N:11]([C:14]4[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=4[CH3:21])[C:12](=[O:13])[C:4]=3[CH:3]=2)=[CH:35][N:34]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 591984044-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine2×HCID 867031692-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one2×

Product 1

HCID 72206457HCID 72206457, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A degassed mixture of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate B) (0.314 mmol), 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (Intermediate U) (0.627 mmol), PdCl2(dppf).CH2Cl2 adduct (0.047 mmol) and K3PO4 (1.255 mmol) in 3:1 dioxane/H2O (4 mL) was heated at 100° C. for 30 min. After cooling to rt, the reaction mixture was diluted with H2O and extracted with EtOAc (2×). The combined organic phases were washed successively with H2O and brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC (prep-HPLC 1) and then triturated in Et2O to afford the title compound as a white solid. ESI-MS: tR=1.21 min, [M+H]+ 522/524/526 (LC-MS 1); 1H-NMR (d6-DMSO, 600 MHz): 7.93 (s, 1H), 7.76 (s, 1H), 7.37 (m, 2H), 7.24 (m, 2H), 7.14 (m, 1H), 7.10 (m, 1H), 6.89 (s, 2H), 6.47 (s, 1H), 6.22 (s, 1H), 3.94 (m, 1H), 3.80 (s, 3H), 1.92 (s, 3H), 1.29 (m, 3H), 0.49 (m, 3H).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic phases were washed successively with H2O and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC (prep-HPLC 1)
  6. customtriturated in Et2O

Sources & evidence

ORD record
ord-122ec30053bc4b6095659b2a033f7ad7
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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