Triethylamine → Tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate

HRID 2199899Notes

Reaction equation

HRID 2199899 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[Cl:43][C:44]1[CH:53]=[CH:52][C:51]2[C:46](=[CH:47][C:48]([N:54]3[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]3)=[CH:49][N:50]=2)[N:45]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:14])([CH3:13])[C:10]([N:57]1[CH2:58][CH2:59][N:54]([C:48]2[CH:49]=[N:50][C:51]3[C:46]([CH:47]=2)=[N:45][C:44]([Cl:43])=[CH:53][CH:52]=3)[CH2:55][CH2:56]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 866975582-Chloro-7-(piperazin-1-yl)-1,5-naphthyridine

Product 1

HCID 88874322Tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamateYield 75.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 2-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid (180 mg, 0.89 mmol, 1.5 eq), triethylamine (209 mg, 2.07 mmol, 3.5 eq) and HOBt (120 mg, 0.89 mmol, 1.5 eq) in anhydrous CH2Cl2 (10 mL), EDCI (170 mg, 0.89 mmol, 1.5 eq) was added. The resulting mixture was stirred at RT for 30 min, and then 2-chloro-7-(piperazin-1-yl)-1,5-naphthyridine (D-19) (0.59 mmol, 1.0 eq) was added. The reaction mixture was stirred at RT for 20 h, and then quenched with water (30 mL) and CH2Cl2 (15 mL), and the organic layer was separated. The organic layer was washed with brine (10 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (2% MeOH—CH2Cl2) to afford the desired product, tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate (D-20) (193 mg, 75.4% yield, 2 steps). ESI-MS m/z: 434.18[M+H]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at RT for 20 h
  3. customquenched with water (30 mL) and CH2Cl2 (15 mL)
  4. customthe organic layer was separated
  5. washThe organic layer was washed with brine (10 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customThe resultant residue was purified by silica gel column chromatography (2% MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-4ea80665c35445b88d970e32171b7771
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

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