Methylamine → 4-[6-(4-Chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-4,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-5-yl]-piperidine-1-carboxylic acid methylamide

HRID 2204381Notes

Reaction equation

HRID 2204381 reaction equation
ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[C:25]3[N:26]([CH:39]([CH3:41])[CH3:40])[C:27]([C:29]4[C:30]([O:37][CH3:38])=[N:31][C:32]([O:35][CH3:36])=[N:33][CH:34]=4)=[CH:28][C:24]=3[C:23](=[O:42])[N:22]2[CH:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)=[CH:17][CH:16]=1.C[CH2:50][N:51]([CH2:54]C)CC.CN>C(Cl)Cl.CCOC(C)=O>[CH3:50][NH:51][C:54]([N:46]1[CH2:47][CH2:48][CH:43]([N:22]2[C:23](=[O:42])[C:24]3[CH:28]=[C:27]([C:29]4[C:30]([O:37][CH3:38])=[N:31][C:32]([O:35][CH3:36])=[N:33][CH:34]=4)[N:26]([CH:39]([CH3:41])[CH3:40])[C:25]=3[CH:21]2[C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)[CH2:44][CH2:45]1)=[O:3]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 867031846-(4-Chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5-piperidin-4-yl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Product 1

HCID 867031874-[6-(4-Chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-4,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-5-yl]-piperidine-1-carboxylic acid methylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

p-Nitrophenyl chloroformate [7693-46-1] (0.339 mmol) was added to a solution of 6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5-piperidin-4-yl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Example 106) (0.242 mmol) and Et3N (0.726 mmol) in CH2Cl2 (2 mL). After stirring at rt for 30 min, the reaction mixture was treated with methylamine (2M/THF) (3.63 mmol) and warmed to 35° C. After 20 h, the reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of NaHCO3 (3×). The organic phase was dried (MgSO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a white solid. tR: 4.93 min (HPLC 4); ESI-MS: tR=0.98 min, [M+H]+ 553/555 (LC-MS 1).

Workup

  1. temperaturewarmed to 35° C
  2. waitAfter 20 h
  3. washwashed with a saturated aqueous solution of NaHCO3 (3×)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-7bb843917f584044812e59a68282c6b8
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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