Morpholine → HCID 178477894, compound

HRID 1842498Notes

Reaction equation

HRID 1842498 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:27]=[CH:26][C:11]2[NH:12][C:13]([CH:15]3[CH2:18][N:17]([C:19]4[CH:24]=[CH:23][N:22]=[C:21](Cl)[N:20]=4)[CH2:16]3)=[N:14][C:10]=2[CH:9]=1.C(OC(N1CC(C(O)=O)C1)=O)(C)(C)C.C(OCC)(=O)C>CC(N(C)C)=O.O>[Cl:7][C:8]1[CH:27]=[CH:26][C:11]2[NH:12][C:13]([CH:15]3[CH2:16][N:17]([C:19]4[CH:24]=[CH:23][N:22]=[C:21]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[N:20]=4)[CH2:18]3)=[N:14][C:10]=2[CH:9]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 178477893HCID 178477893, compound

Product 1

HCID 178477894HCID 178477894, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of morpholine (0.19 mL, 2.19 mmol) and 5-chloro-2-(1-(2-chloropyrimidin-4-yl)azetidin-3-yl)-1H-benzo[d]imidazole, as prepared according to Example 1a, but using 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid in place of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester, (0.069 g, 0.22 mmol) in DMA (1 mL) under argon was heated to 75° C. for 5 h, then cooled to RT. Ethyl acetate and water were added, the resulting layers were separated, and the organic layer was washed with water (2×), brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil. The oil was purified by silica gel chromatography to give 4-(4-(3-(5-chloro-1H-benzo[d]imidazol-2-yl)azetidin-1-yl)pyrimidin-2-yl)morpholine (0.068 g, 0.18 mmol, 84% yield) as a white solid. [M+1] 371. IC50 (uM) 0.645.

Workup

  1. customas prepared
  2. temperaturecooled to RT
  3. customthe resulting layers were separated
  4. washthe organic layer was washed with water (2×), brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an oil
  9. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b03d5fbe4cc7449a98413dce6e62696e
Source dataset
uspto-grants-2015_02
Patent number
US08946230B2

Reaction notes

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