1,1'-Carbonyldiimidazole → 1-[(2-isopropoxy-6-methyl-3-pyridyl)methyl]-3-(3-oxo-4H-1,4-benzoxazin-8-yl)urea

HRID 1505229Notes

Reaction equation

HRID 1505229 reaction equation
[CH:1]([O:4][C:5]1[C:10]([CH2:11][NH2:12])=[CH:9][CH:8]=[C:7]([CH3:13])[N:6]=1)([CH3:3])[CH3:2].C1N=CN([C:19](N2C=NC=C2)=[O:20])C=1.[NH2:26][C:27]1[C:32]2[O:33][CH2:34][C:35](=[O:37])[NH:36][C:31]=2[CH:30]=[CH:29][CH:28]=1>C1COCC1.CN(C=O)C>[CH:1]([O:4][C:5]1[C:10]([CH2:11][NH:12][C:19]([NH:26][C:27]2[C:32]3[O:33][CH2:34][C:35](=[O:37])[NH:36][C:31]=3[CH:30]=[CH:29][CH:28]=2)=[O:20])=[CH:9][CH:8]=[C:7]([CH3:13])[N:6]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 61655597[2-Isopropoxy-6-methyl-3-pyridyl]methanamine

Product 1

HCID 534767031-[(2-isopropoxy-6-methyl-3-pyridyl)methyl]-3-(3-oxo-4H-1,4-benzoxazin-8-yl)ureaYield 21%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 33a (1.14 g, 6.35 mmol) in THF (30 mL) was added CDI (2.1 mol eq, 2.16 g) and the mixture was heated at 70° C. for 6 h. The reaction mixture was evaporated, water was added and the aqueous phase was extracted with EtOAc (3×35 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure (yellow oil, 1.61 g, 93% yield). The oil obtained (0.34 g, 1.25 mmol) was dissolved in DMF (20 mL) and the bicyclic amine 1f was added (0.8 mol eq, 0.20 g), then the mixture obtained was heated at 100° C. overnight. The solvent was removed at reduced pressure and the residue was purified by chromatography (1:1 EtOAc:Petroleum ether) to obtain the product as a white solid (0.07 g, 21% Yield). 1HNMR (DMSO, 400 MHz) δ 1.28 (s, 3H), 1.31 (s, 3H), 2.34 (s, 3H), 4.14 (d, 2H, J=6), 4.60 (s, 2H), 5.25 (m, 1H), 6.48 (dd, 1H), 6.77 (m, 2H), 7.11 (t, 1H), 7.44 (d, 1H, J=8), 7.71 (dd, 1H), 8.16 (s, 1H), 10.64 (bs, 1H). [M+1] 370.95 (C19H22N4O4 requires 370.40).

Workup

  1. customThe reaction mixture was evaporated
  2. additionwater was added
  3. extractionthe aqueous phase was extracted with EtOAc (3×35 mL)
  4. customevaporated at reduced pressure (yellow oil, 1.61 g, 93% yield)
  5. customThe oil obtained (0.34 g, 1.25 mmol)
  6. custom0.20 g), then the mixture obtained
  7. temperaturewas heated at 100° C. overnight
  8. customThe solvent was removed at reduced pressure
  9. customthe residue was purified by chromatography (1:1 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-40a52ea9dd24487d84cdeb0824231b30
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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