1,1'-Carbonyldiimidazole → HCID 53476814, compound

HRID 1505231Notes

Reaction equation

HRID 1505231 reaction equation
[N:1]1([C:6]2[C:11]([CH2:12][NH2:13])=[CH:10][CH:9]=[C:8]([C:14]([F:17])([F:16])[F:15])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1N=CN([C:23]([N:25]2C=N[CH:27]=[CH:26]2)=[O:24])C=1.NC1C2[O:37][CH2:38][C:39](=[O:41])[NH:40][C:35]=2[CH:34]=[CH:33][CH:32]=1>C1COCC1.CN(C=O)C>[O:41]=[C:39]1[NH:40][C:35]2[CH:34]=[CH:33][CH:32]=[C:26]([NH:25][C:23]([NH:13][CH2:12][C:11]3[C:6]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[N:7][C:8]([C:14]([F:17])([F:15])[F:16])=[CH:9][CH:10]=3)=[O:24])[C:27]=2[O:37][CH2:38]1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 58873689HCID 58873689, compound

Product 1

HCID 53476814HCID 53476814, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(1-pyrrolidinyl)-6-(trifluoromethyl)-3-aminomethyl-pyridine 29e (0.58 g, 2.3 mmol) in THF (25 mL) was added CDI (2.1 mol eq, 0.77 g) and the mixture was heated for 5 h. The reaction mixture was evaporated, water was added and the aqueous phase was extracted with EtOAc (3×20 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure. The oil obtained (0.51 g, 1.52 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 (0.12 g, 24% Yield). 1HNMR (DMSO, 400 MHz) δ 1.89 (m, 4H), 3.56 (m, 4H), 4.41 (d, 2H, J=6), 4.61 8s, 2H), 6.46 (dd, 1H, J=2), 6.80 (t, 1H, J=8), 7.12 (d, 1H, J=8), 7.25 (t, 1H), 7.70 (m, 2H), 8.17 (bs, 1H), 10.66 (bs, 1H). [M+1] 436.03 (C20H20F3N5O3 requires 435.40).

Workup

  1. temperature0.77 g) and the mixture was heated for 5 h
  2. customThe reaction mixture was evaporated
  3. additionwater was added
  4. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  5. customevaporated at reduced pressure
  6. customThe oil obtained (0.51 g, 1.52 mmol)
  7. custom0.20 g), then the mixture obtained
  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-ca56319470e2454592ed0054d61ca9da
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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