Diisopropylethylamine → HCID 73053992, compound

HRID 1846214Notes

Reaction equation

HRID 1846214 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@:14]2([NH2:24])[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[O:17][CH2:16][CH2:15]2)[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11].[O:25]=[C:26]1[C:35](=[O:36])[NH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([C:37](Cl)=[O:38])[CH:32]=2)[NH:27]1.CCN(C(C)C)C(C)C>C(Cl)Cl.O.CCOC(C)=O>[F:2][C:3]1[CH:4]=[C:5]([C@:14]2([NH:24][C:37]([C:31]3[CH:32]=[C:33]4[C:28](=[CH:29][CH:30]=3)[NH:27][C:26](=[O:25])[C:35](=[O:36])[NH:34]4)=[O:38])[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[O:17][CH2:16][CH2:15]2)[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:11])[F:12]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 89964297HCID 89964297, compoundHCID 899649682,3-Dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl chloride

Product 1

HCID 73053992HCID 73053992, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (0.300 g, 1.455 mmol) in DCM (3 mL) was added oxalyl chloride (0.387 mL, 4.37 mmol) and a drop of DMF (anhydrous). The resulting mixture was then stirred at room temperature for 2 h, then the mixture was concentrated in vacuo to give 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl chloride. A solution of (S)-4-(3-fluoro-4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine hydrochloride (50 mg, 0.137 mmol) in DCM (1 mL) at 0° C. was added 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl chloride (326 mg, 1.453 mmol), and DIEA (0.072 mL, 0.411 mmol). The resulting mixture was stirred at 0° C. for 30 min and then at room temperature for overnight. The reaction was diluted with H2O (5 mL) and EtOAc (7 mL). The mixture was then stirred at room temperature for 30 min. The mixture was then filtered and the organic layer was dried over MgSO4, and concentrated in vacuo. The residue was dissolved in DMSO (2 mL) and solution was purified by preparative HPLC (0-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 517.0 (MH+). 1H NMR (400 MHz, d4-MeOH) δ: 8.27 (dd, J=4.8, 1.3 Hz, 1H), 7.60-7.69 (m, 3H), 7.51-7.58 (m, 1H), 7.42-7.48 (m, 2H), 7.24 (d, J=8.4 Hz, 2H), 4.45-4.59 (m, 1H), 4.16-4.35 (m, 1H), 3.07-3.27 (m, 1H), 2.84-3.05 (m, 1H).

Workup

  1. waitat room temperature for overnight
  2. stirringThe mixture was then stirred at room temperature for 30 min
  3. filtrationThe mixture was then filtered
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DMSO (2 mL)
  7. customsolution was purified by preparative HPLC (0-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-6cd6f274323e4080a592bebe868a1988
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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