Triethylamine → HCID 11362921, compound

HRID 1833273Notes

Reaction equation

HRID 1833273 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)=[N:8][CH:7]=[C:6]2[C:25]([OH:27])=O.C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[OH:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(OCC)(=O)C.CN(C)C=O>[OH:43][CH:44]1[CH2:49][CH2:48][N:47]([C:25]([C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]([C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=3)=[O:24])=[N:8][CH:7]=2)=[O:27])[CH2:46][CH2:45]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 79341Piperidin-4-olHCID 11394498HCID 11394498, compound

Product 1

HCID 11362921HCID 11362921, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6,7-dimethoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid (30.0 mg, 61.75 mmol) in dry, N,N-dimethylformamide (2 mL) was chilled in an ice bath under argon. With stirring, triethylamine (14.4 uL, 102 mmol) and isobutylchloroformate (13.4 uL, 102 mmol) were added. The solution was stirred for 30 min and then 4-hydroxypiperidine (165 mg, 1.633 mmol) was added. The solution was allowed to warm to room temperature with stirring for 1 hr. and then diluted with ethyl acetate (30 mL). The ethyl acetate solution was washed sequentially with saturated aqueous sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated aqueous sodium chloride solution (5 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to afford 35 mg of an off white solid. This crude material was purified by flash chromatography eluting with 50% ethyl acetate in hexanes (containing 1% acetic acid) and then increasing gradually to 80% ethyl acetate in hexanes. After tlc analysis, fractions were pooled and evaporated to yield 25 mg (68%) of product as an acetic acid salt: APCI-MS m/e calcd for C25H26N2O6 (M+H) 451.5, found 451, H NMR (300 MHz) compatible.

Workup

  1. stirringThe solution was stirred for 30 min
  2. stirringwith stirring for 1 hr
  3. washThe ethyl acetate solution was washed sequentially with saturated aqueous sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated aqueous sodium chloride solution (5 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford 35 mg of an off white solid
  8. customThis crude material was purified by flash chromatography
  9. washeluting with 50% ethyl acetate in hexanes (containing 1% acetic acid)
  10. temperatureincreasing gradually to 80% ethyl acetate in hexanes
  11. customevaporated

Sources & evidence

ORD record
ord-1ac816ff451e4e6291e048ea950d5da2
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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