Morpholine → [2-(Morpholine-4-carbonyl)-pyridin-4-yl]-carbamic acid tert-butyl ester

HRID 55886Notes

Reaction equation

HRID 55886 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]([OH:17])=O)[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])[CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 497603724-(((Tert-butoxy)carbonyl)amino)pyridine-2-carboxylic acid

Product 1

HCID 90356783[2-(Morpholine-4-carbonyl)-pyridin-4-yl]-carbamic acid tert-butyl esterYield 93.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 4-tert-butoxycarbonylamino-pyridine-2-carboxylic acid (43) (800 mg, 3.2 mmol) in CHCl3 was added morpholine (0.4 mL, 3.8 mmol), HOBT (857 mg, 6.3 mmol), EDC.HCl (1.2 g, 6.3 mmol) and DIPEA (0.8 mL, 4.8 mmol), and stirred at rt for 16 h. The reaction mixture was diluted with water and extracted with 10% MeOH/CHCl3. The organic layer was washed with water, dried over Na2SO4 and evaporated to give compound 44 (920 mg, 92%) as a white solid; (m/z): 308 [MH]+; 1H NMR (400 MHz, CDCl3): δ 8.40 (1H, d, J=5.6 Hz), 7.57 (1H, d, J=2.0 Hz), 7.54 (1H, d, J=5.6 Hz), 6.98 (1H, br s), 3.79 (4H, m), 3.67-3.66 (4H, m), 1.53 (9H, s).

Workup

  1. extractionextracted with 10% MeOH/CHCl3
  2. washThe organic layer was washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-64536afbf0dd4ae790a618f465ca584b
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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