Triethylamine → (S)-tert-butyl 3-(6-(difluoromethoxy)pyridin-3-yl)-3-(1-(2,2-dimethoxyethyl)-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)ureido)propanoate

HRID 1396833Notes

Reaction equation

HRID 1396833 reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[N:9]=[CH:8][C:7]([C@@H:10]([NH:19][CH2:20][CH:21]([O:24][CH3:25])[O:22][CH3:23])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:6][CH:5]=1.ClC(Cl)(O[C:31](=[O:37])OC(Cl)(Cl)Cl)Cl.CCN(CC)CC.[N:46]1[C:55]2[NH:54][CH2:53][CH2:52][CH2:51][C:50]=2[CH:49]=[CH:48][C:47]=1[CH2:56][CH2:57][CH2:58][NH2:59]>C(Cl)Cl.ClCCCl>[F:26][CH:2]([F:1])[O:3][C:4]1[N:9]=[CH:8][C:7]([C@@H:10]([N:19]([CH2:20][CH:21]([O:24][CH3:25])[O:22][CH3:23])[C:31]([NH:59][CH2:58][CH2:57][CH2:56][C:47]2[CH:48]=[CH:49][C:50]3[CH2:51][CH2:52][CH2:53][NH:54][C:55]=3[N:46]=2)=[O:37])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 98775993-(5,6,7,8-Tetrahydro-1,8-naphthyridin-2-yl)propan-1-amineHCID 90311798HCID 90311798, compound

Product 1

HCID 90311875(S)-tert-butyl 3-(6-(difluoromethoxy)pyridin-3-yl)-3-(1-(2,2-dimethoxyethyl)-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)ureido)propanoateYield 68.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of compound 8 (375 mg, 0.99 mmol, 1.0 equiv.) in dry DCM (5 mL), cooled to 0° C., triphosgene (1.50 mL, 2.99 mmol, 3.00 equiv., 20% in PhMe) followed by Et3N (0.30 mL, 2.09 mmol, 2.10 equiv) were added. The reaction mixture was slowly brought to RT and stirred for 2 h. After completion of the starting material, volatiles were evaporated to afford the crude compound 9, which was used directly in the next step without purification. A solution of compound 9 in DCE (2 mL) was added to a solution of compound 6b (400 mg, 1.32 mmol, 1.32 equiv.) in DCM (5 mL), Et3N (0.55 mL, 3.98 mmol, 4.00 equiv) at 0° C. and stirred at RT for 4 h. After consumption of the starting material (monitored by TLC), the reaction mixture was concentrated under reduced pressure to give the crude residue which was purified by column chromatography (2% MeOH/DCM) to afford compound 10 (0.40 g, 67%) as a thick syrup.

Workup

  1. additionwere added
  2. customwas slowly brought to RT
  3. customAfter completion of the starting material, volatiles were evaporated
  4. customto afford the crude compound 9, which
  5. customwas used directly in the next step without purification
  6. stirringstirred at RT for 4 h
  7. customAfter consumption of the starting material (monitored by TLC)
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. customto give the crude residue which
  10. customwas purified by column chromatography (2% MeOH/DCM)

Sources & evidence

ORD record
ord-87eb0f9592c5425cbdc9b85fa5b7ea1c
Source dataset
uspto-grants-2014_12
Patent number
US08901144B2

Reaction notes

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