Diisopropylethylamine → HCID 10983515, compound

HRID 429050Notes

Reaction equation

HRID 429050 reaction equation
Cl[C:2]1[C:3]2[C:18]3[CH:19]=[N:20][N:21]([CH2:22][CH3:23])[C:17]=3[N:16]=[CH:15][C:4]=2[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[N:6][N:7]=1.Cl.[Cl:25][C:26]1[CH:27]=[C:28]([CH2:34][NH2:35])[CH:29]=[CH:30][C:31]=1[O:32][CH3:33].C(N(C(C)C)CC)(C)C.ClCCl.CO>CN1CCCC1=O>[Cl:25][C:26]1[CH:27]=[C:28]([CH2:34][NH:35][C:2]2[C:3]3[C:18]4[CH:19]=[N:20][N:21]([CH2:22][CH3:23])[C:17]=4[N:16]=[CH:15][C:4]=3[C:5]([N:8]3[CH2:9][CH2:10][CH:11]([OH:14])[CH2:12][CH2:13]3)=[N:6][N:7]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27642873-Chloro-4-methoxybenzylamine hydrochlorideHCID 20703336HCID 20703336, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 10983515HCID 10983515, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-(9-Chloro-3-ethyl-3H-pyrazolo-[4′,3′:5,6]pyrido-[3,4-d]pyridazin-6-yl)-4-piperidinol (2.4 g, 7.2 mmol) and (3-chloro-4-methoxyphenyl)methylamine hydrogen chloride (7.5 g, 5 eq) were suspended in N-methylpyrrolidinone (20 mL) and diisopropylethylamine (5 eq) in a 100 mL pressure tube. The reaction tube was submerged in a preheated oil bath at 170° C. for 2 h. HPLC analysis showed complete consumption of starting material. The reaction was cooled to rt and diluted with EtOAc (250 mL). This solution was washed consecutively with water (200 mL×3) and brine (200 mL×2) and dried over sodium sulfate. The solvent was removed via evaporation under reduced pressure to afford a brown foam. Column chromatography of this foam using silica gel and dichloromethane-methanol (30:1) afforded the title compound as an orange solid (2.0 g, 60%): mp 109-110.5° C. The material was analyzed by HPLC and showed 95% purity: HPLC (YMC S5 ODS 4.6×50 mm column, 4 minute gradient-0% B to 100% B, 4 mL/min flow, solvent A: 10% MeOH-90% H2O-0.2% H3PO4, solvent B: 90% MeOH-10% H2O-0.2% H3PO4) retention time 3.22 minutes; LRMS (m/z) 468 (MH+).

Workup

  1. customconsumption of starting material
  2. additiondiluted with EtOAc (250 mL)
  3. washThis solution was washed consecutively with water (200 mL×3) and brine (200 mL×2)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed via evaporation under reduced pressure
  6. customto afford a brown foam

Sources & evidence

ORD record
ord-3de431c58089487a929d8b85170171bd
Source dataset
uspto-grants-2001_11
Patent number
US06316438B1

Reaction notes

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