Ethanol → 2-Cyano-N-{(3R)-1-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]pyrrolidin-3-yl}-N-methylacetamide

HRID 589128Notes

Reaction equation

HRID 589128 reaction equation
[CH2:1]([N:3](CC)CC)C.[CH2:8]([OH:10])[CH3:9].[CH3:11][C:12]1[C:16]([C:17]2[C:26]3[O:25][CH2:24][C@H:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[N:22]4[C:33]([N:35]5[CH2:39][CH2:38][C@@H:37]([NH:40][CH3:41])[CH2:36]5)=[N:34][C:20]([C:21]=34)=[CH:19][CH:18]=2)=[C:15]([CH3:42])[O:14][N:13]=1.O=C1CCC(=O)N1OC(=O)CC#N>C(Cl)Cl.CO>[C:1]([CH2:9][C:8]([N:40]([C@@H:37]1[CH2:38][CH2:39][N:35]([C:33]2[N:22]3[C@@H:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:24][O:25][C:26]4=[C:21]3[C:20](=[CH:19][CH:18]=[C:17]4[C:16]3[C:12]([CH3:11])=[N:13][O:14][C:15]=3[CH3:42])[N:34]=2)[CH2:36]1)[CH3:41])=[O:10])#[N:3]

Participants

7

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 534158962,5-Dioxopyrrolidin-1-yl 2-cyanoacetateHCID 86299192US9624241, Example 181A

Product 1

HCID 904090432-Cyano-N-{(3R)-1-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]pyrrolidin-3-yl}-N-methylacetamideYield 14%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (8.2 μL, 0.059 mmol) and ethanol (1.0 mL) were added to a solution of (3R)-1-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]-N-methylpyrrolidin-3-amine (8.5 mg, 0.020 mmol) in methylene chloride (0.50 mL), followed by addition of 3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropanenitrile (7.2 mg, 0.039 mmol) and the mixture was stirred overnight at room temperature. The mixture was then diluted with methanol and purified by preparative LCMS using pH 10 buffer to give the title compound (1.4 mg, 14%). LCMS calc. for C27H28N7O3 (M+H)+: m/z=498.2. found: 498.3.

Workup

  1. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-aee47cb462604651bd552eefe8132253
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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