Diisopropylethylamine → HCID 25230750, compound

HRID 657587Notes

Reaction equation

HRID 657587 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:3]=1.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.C(N(CC)C(C)C)(C)C.[Cl:41][C:42]1[CH:43]=[C:44]([N:62]2[C:67](=[O:68])[NH:66][C:65](=[O:69])[C:64]([C:70]#[N:71])=[N:63]2)[CH:45]=[C:46]([Cl:61])[C:47]=1[O:48][C:49]1[CH:54]=[C:53]([CH:55]([CH3:57])[CH3:56])[C:52](=[O:58])[N:51]([CH2:59]O)[N:50]=1>C(Cl)Cl>[Cl:61][C:46]1[CH:45]=[C:44]([N:62]2[C:67](=[O:68])[NH:66][C:65](=[O:69])[C:64]([C:70]#[N:71])=[N:63]2)[CH:43]=[C:42]([Cl:41])[C:47]=1[O:48][C:49]1[CH:54]=[C:53]([CH:55]([CH3:56])[CH3:57])[C:52](=[O:58])[N:51]([CH2:59][O:10][C:9](=[O:11])[CH2:8][C:4]2[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=2)[N:50]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27237243-Pyridineacetic acid, hydrochloride (1:1)HCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 25230624HCID 25230624, compound

Product 1

HCID 25230750HCID 25230750, compoundYield 22.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of pyridin-3-yl-acetic acid hydrochloride salt (57.3 mg, 0.33 mmol) in methylene chloride (1.84 mL) was treated with N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (119 mg, 0.39 mmol) and N,N-diisopropylethylamine (0.17 mL, 0.99 mmol). The resulting solution was stirred at 25° C. for 2.5 h. At this time, 2-[3,5-dichloro-4-(1-hydroxymethyl-5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (200 mg, 0.42 mmol) was added to the reaction. The reaction mixture was stirred at 25° C. for 18 h. At this time, the reaction mixture was diluted with methylene chloride (50 mL) and washed with water (3×150 mL). The organics were dried over sodium sulfate, filtered, rinsing with methylene chloride and concentrated in vacuo. Biotage flash chromatography (40S, 1-4% methanol/methylene chloride) followed by supercritical fluid chromatography (Daicel OD column, 60% methanol) afforded pyridin-3-yl-acetic acid 3-[2,6-dichloro-4-(6-cyano-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-5-isopropyl-6-oxo-6H-pyridazin-1-ylmethyl ester (43.2 mg, 22%) as a yellow solid. ES+-HRMS m/e calcd for C25H19N7O6Cl2 (M+H+) 584.0847, found 584.0848.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 18 h
  2. washwashed with water (3×150 mL)
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. washrinsing with methylene chloride
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f819b56d2555486a87fdc3e884507761
Source dataset
uspto-grants-2011_12
Patent number
US08076334B2

Reaction notes

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