Diisopropylethylamine → HCID 178514926, compound

HRID 2369929Notes

Reaction equation

HRID 2369929 reaction equation
[N:1]12[CH2:8][CH2:7][C:4]([CH2:9][NH:10][CH2:11][C:12]3[C:20]4[C:19]([C:21]([O-])=[O:22])=[CH:18][CH:17]=[CH:16][C:15]=4[NH:14][N:13]=3)([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[Li+].C(N(CC)C(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C1COCC1>[N:1]12[CH2:8][CH2:7][C:4]([CH2:9][N:10]3[CH2:11][C:12]4=[N:13][NH:14][C:15]5[C:20]4=[C:19]([CH:18]=[CH:17][CH:16]=5)[C:21]3=[O:22])([CH2:3][CH2:2]1)[CH2:5][CH2:6]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 178524261HCID 178524261, compound

Product 1

HCID 178514926HCID 178514926, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium 3-((quinuclidin-4-ylmethylamino)methyl)-1H-indazole-4-carboxylate (3.9 g, 12.1 mmol) from Step B above in THF (20 mL) was cooled in an ice bath while N,N-diisopropylethylamine (9.4 g, 72.8 mmol) was added, followed by 1-propanephosphonic acid cyclic anhydride (T3P) (23.0 g, 72.8 mmol). The reaction mixture was stirred at room temperature for 5 h and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 60:36:4 dichloromethane/methanol/concentrated ammonium hydroxide) to give 4-(quinuclidin-4-ylmethyl)-3,4-dihydropyrazolo[3,4,5-de]isoquinolin-5(1H)-one as a yellow oil (468 mg, 13%): 1H NMR (500 MHz, CD3OD) δ 7.62-7.60 (m, 1H), 7.54-7.53, (m, 2H), 5.15 (s, 2H), 3.53 (s, 2H), 2.93 (t, J=8.0 Hz, 6H), 1.67 (t, J=8.0 Hz, 6H); MS (ESI+) m/z 297 (M+H).

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. customThe crude material was purified by column chromatography (silica gel, 60:36:4 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-51cae366743e4a97b71616b73f8dc3a7
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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