Morpholine-4-carboximidamide Hydrobromide → HCID 178451771, compound

HRID 1801553Notes

Reaction equation

HRID 1801553 reaction equation
Br.[N:2]1([C:8]([NH2:10])=[NH:9])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([C:24](=O)[CH2:25][C:26](OCC)=[O:27])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[N+](=C1CCCCCCCCCC1C1CCCCCCCCCC1)=[N-]>C(O)C>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH2:20][CH:21]([C:24]2[CH:25]=[C:26]([OH:27])[N:10]=[C:8]([N:2]3[CH2:7][CH2:6][O:5][CH2:4][CH2:3]3)[N:9]=2)[CH2:22][CH2:23]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 2806564Morpholine-4-carboximidamide HydrobromideHCID 6618868tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylateHCID 22171225HCID 22171225, compound

Product 1

HCID 178451771HCID 178451771, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Morpholine-4-carboxamidine hydrobromide (0.267 g) and 4-(2-ethoxycarbonylacetyl)-piperidine-1-carboxylic acid tert-butyl ester (0.38 g, 1.27 mmol) were stirred in ethanol (10 mL) and diazobicycloundecane (285 μl) was added. The reaction stirred for 18 hours at room temperature. The ethanol was removed under reduced pressure and water (25 mL) was added. The solution was acidified (to pH=4) with acetic acid. The product was extracted with dichloromethane (4×30 mL). The dichloromethane was removed and crude product was purified twice on silica gel (Combiflash), eluting with 10% methanol in dichloromethane to provide 4-(6-hydroxy-2-morpholin-4-ylpyrimidin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.15 g, 40.5% yield) as a white solid. 1H NMR (300 MHz, CDCl3/TMS): δ=5.63 (s, 1H), 4.25-4.05 (m, 2H), 3.75 (m, 8H), 2.75-2.65 (m, 2H), 2.47-2.35 (m, 1H), 1.00-1.75 (m, 2H), 1.70-1.50 (m, 2H), 1.46 (s, 9H). 13C NMR (75 MHz, CDCl3/TMS): δ=173.35, 166.87, 154.96, 154.06, 98.88, 79.70, 66.72, 45.13, 44.24, 30.64, 28.82, 27.58.

Workup

  1. customThe ethanol was removed under reduced pressure and water (25 mL)
  2. additionwas added
  3. extractionThe product was extracted with dichloromethane (4×30 mL)
  4. customThe dichloromethane was removed
  5. customcrude product was purified twice on silica gel (Combiflash)
  6. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-b3c6f987df6e4348ac105b018838cda3
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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