Morpholine → HCID 178510416, compound

HRID 1054262Notes

Reaction equation

HRID 1054262 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3([CH:19]=O)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=[CH:9][C:8]=2[NH:21][C:22]([C:24]2[NH:25][CH:26]=[C:27]([C:29]#[N:30])[N:28]=2)=[O:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1>[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3([CH2:19][N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=[CH:9][C:8]=2[NH:21][C:22]([C:24]2[NH:25][CH:26]=[C:27]([C:29]#[N:30])[N:28]=2)=[O:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 178510421HCID 178510421, compound

Product 1

HCID 178510416HCID 178510416, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A mixture of 4-cyano-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(4-formyl-tetrahydro-pyran-4-yl)-phenyl]-amide (as prepared in the previous step, 30.5 mg, 0.0754 mmol), morpholine (14 μL, 0.15 mmol) and sodium borohydride (6.0 mg, 0.16 mmol) in 2 mL of 1:1 DCM/THF was stirred at RT for 3 h. The mixture was then treated with saturated NaHCO3 aqueous solution (10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL). After drying over Na2SO4 and concentrating in vacuo, the residue was purified by silica gel chromatography (10-30% EtOAc/DCM) to afford the title compound (28 mg, 77%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 12.61 (s, 1H), 9.66 (s, 1H), 8.31 (d, 1H, J=8.6 Hz), 7.76 (s, 1H), 7.28 (dd, 1H, J=8.6, 2.3 Hz), 7.17 (d, 1H, J=2.3 Hz), 5.86 (m, 1H), 3.79 (m, 2H), 3.59 (m, 2H), 3.53 (m, 4H), 2.45 (s, 2H), 2.29 (m, 4H), 2.13-2.21 (m, 6H), 1.77-1.98 (m, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H33N5O3, 476.3 (M+H). found 476.2.

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
  3. dry with materialAfter drying over Na2SO4
  4. concentrationconcentrating in vacuo
  5. customthe residue was purified by silica gel chromatography (10-30% EtOAc/DCM)

Sources & evidence

ORD record
ord-a291bcf6eb06435f8e5f887d87181b96
Source dataset
uspto-grants-2016_07
Patent number
US09394289B2

Reaction notes

Loading…