1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [3-(4-Amino-1-methyl-2-oxo-1,2-dihydro-[1,8]naphthyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester

HRID 2244812Notes

Reaction equation

HRID 2244812 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([C:18]([OH:20])=O)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[NH2:31][C:32]1[C:33](=[O:44])[N:34]([CH3:43])[C:35]2[C:40]([C:41]=1[NH2:42])=[CH:39][CH:38]=[CH:37][N:36]=2.CCN=C=NCCCN(C)C>CN(C=O)C.O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([C:18](=[O:20])[NH:31][C:32]2[C:33](=[O:44])[N:34]([CH3:43])[C:35]3[C:40]([C:41]=2[NH2:42])=[CH:39][CH:38]=[CH:37][N:36]=3)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 446300243-{[(Benzyloxy)carbonyl]amino}cyclohexane-1-carboxylic acidHCID 451232963,4-Diamino-1-methyl-1,8-naphthyridin-2(1H)-one

Product 1

HCID 45123295[3-(4-Amino-1-methyl-2-oxo-1,2-dihydro-[1,8]naphthyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl esterYield 12.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Benzyloxycarbonylamino-cyclohexanecarboxylic acid (0.277 g, 1.0 mmol), TEA (0.10 g, 1.0 mmol), and HOBt (0.135 g, 1.0 mmol) were added sequentially to a stirred solution of 3,4-diamino-1-methyl-1H-[1,8]naphthyridin-2-one (0.19 g, 1.0 mmol) in DMF (8 mL) at room temperature. The solution was cooled to 0° C. and EDCI (0.19 g, 1.0 mmol) was added. The resulting solution was allowed to stir, with warming to room temperature, for 17 h. The mixture was diluted with water (5 mL) and extracted with CH2Cl2, dried with MgSO4, and concentrated. The residue was purified by flash chromatography eluting with 5% MeOH in CH2Cl2 to give [3-(4-amino-1-methyl-2-oxo-1,2-dihydro-[1,8]naphthyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester (55 mg, 12% yield), and 60 mg (32%) of unreacted diamine. 1H-NMR (CDCl3): δ 8.59 (m, 1H), 8.21 (m, 1H), 7.91 (m, 1H), 7.33 (m, 6H), 7.20 (dd, 1H, J=8.0, 4.8), 5.51 (m, 2H), 5.12 (m, 2H), 4.76 (m, 1H), 4.10 (m, 1H), 3.81 (s, 3H), 2.60 (m, 1H), 2.33 (m, 1H), 1.93-2.05 (m, 3H), 1.73 (m, 2H), 1.45 (m, 2H). MS: calculated for C24H27N5O4+H 450.2; found: 450.5.

Workup

  1. temperaturewith warming to room temperature, for 17 h
  2. extractionextracted with CH2Cl2
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography
  6. washeluting with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-8b45a7e81931400eb8738fbb0cfc8ba4
Source dataset
uspto-grants-2010_03
Patent number
US07678909B1

Reaction notes

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