Triethylamine → 8-bromo-1-(oxan-4-yl)-3H-imidazo[4,5-c]quinolin-2-one

HRID 1486914Notes

Reaction equation

HRID 1486914 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6](C(O)=O)=[C:5]2[NH:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C([N:24]([CH2:27]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:30]C1C=CC=CC=1>CN(C=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:24][C:27](=[O:30])[N:15]([CH:16]4[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)[C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 1184986206-Bromo-4-(oxan-4-ylamino)quinoline-3-carboxylic acid

Product 1

HCID 1185026328-bromo-1-(oxan-4-yl)-3H-imidazo[4,5-c]quinolin-2-oneYield 101.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

On a larger scale, 6-bromo-4-(oxan-4-ylamino)quinoline-3-carboxylic acid (2011 g, (2005 g active), 5.71 mol) was added to the vessel with DMF (18.2 L). Triethylamine (4.7 L, 33.72 mol) was added with an endotherm observed from 21-18° C. Diphenyl phosphorazidate (1600 mL, 7.42 mol) was added over 10 minutes with an observed exotherm from 21° C. to 23° C. over the addition. The exotherm continued with the batch reaching 55° C. after 1 h (jacket held at 30° C.) with gas evolution. The reaction initially went into solution with a precipitate then forming after ˜30 minutes. Once the temperature had stabilised the batch was analysed by HPLC showing consumption of starting material and 99% product. The batch was heated to 60° C. for h with HPLC again indicating consumption of starting material and 98% product. The batch was concentrated in vacuo to a minimum volume (˜3 volumes) and the residue added to water (17 L) rinsing in with a further portion of water (10 L). The mixture was slurried for 1 h and filtered, washing with water (2×17 L). The solid was then returned to the vessel and slurried in sat. NaHCO3 solution (10 L) and MeOH (495 ml) for 1 h. The solid was collected by filtration, washing with water (2×3.5 L) and then oven dried in vacuo at 40° C. for 116 h to obtain 2023 g of desired material. Analytical data was consistent with that obtained from previous batches.

Workup

  1. customobserved from 21-18° C
  2. custom(jacket held at 30° C.)
  3. customThe reaction
  4. customthen forming after ˜30 minutes
  5. customconsumption of starting material and 99% product
  6. customconsumption of starting material and 98% product
  7. concentrationThe batch was concentrated in vacuo to a minimum volume (˜3 volumes)
  8. additionthe residue added to water (17 L)
  9. washrinsing in with a further portion of water (10 L)
  10. waitThe mixture was slurried for 1 h
  11. filtrationfiltered
  12. washwashing with water (2×17 L)
  13. waitMeOH (495 ml) for 1 h
  14. filtrationThe solid was collected by filtration
  15. washwashing with water (2×3.5 L)
  16. customoven dried in vacuo at 40° C. for 116 h

Sources & evidence

ORD record
ord-504e531d2e4a46bbaf99c887eb4b3380
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

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