Hydrogen Bromide → HCID 59262865, compound

HRID 908335Notes

Reaction equation

HRID 908335 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[S:44][C:22]3=[CH:23][CH:24]=[C:25]4[C:30]([N:29]=[C:28]([NH:31][C:32]5[CH:37]=[CH:36][CH:35]=[C:34]([N:38]6[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]6)[CH:33]=5)[N:27]=[CH:26]4)=[C:21]3[CH:20]=2)=[O:18])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.Br.CO>C(Cl)Cl>[N:14]1([C:17]([C:19]2[S:44][C:22]3=[CH:23][CH:24]=[C:25]4[C:30]([N:29]=[C:28]([NH:31][C:32]5[CH:37]=[CH:36][CH:35]=[C:34]([N:38]6[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]6)[CH:33]=5)[N:27]=[CH:26]4)=[C:21]3[CH:20]=2)=[O:18])[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 887MethanolHCID 59262791HCID 59262791, compound

Product 1

HCID 59262865HCID 59262865, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

4-[2-(3-Piperidin-1-yl-phenylamino)-thieno[2,3-h]quinazoline-8-carbonyl]-piperazine-1-carboxylic acid benzyl ester (205 mg, 0.34 mmol) was dissolved in dry DCM (4 mL) and HBr (2 mL, 33 wt % solution in AcOH) added. The resultant mixture was stirred at room temperature for 0.5 hours and concentrated under reduced pressure. The yellow gum obtained was partitioned between Et2O and dilute HCl. The aqueous layer was extracted with Et2O (1×10 mL). The aqueous layer was then basified with saturated Na2CO3 and extracted with DCM (3×10 mL). The DCM organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The brown gum obtained was redissolved in DCM, silica (˜5 mL) added and concentrated under reduced pressure. The solid obtained was subjected to column chromatography (10% MeOH in DCM, ˜100 mL silica) to give a bright yellow solid. This solid was triturated with Et2O, filtered and washed with Et2O (3×5 mL) and pentane (3×5 mL) to give a yellow powder (96.4 mg, 60% yield). MS (ES+) 473, (ES−) 472. δH (CDCl3) 1.5-1.9 (6H, m), 2.9-3.1 (4H, m), 3.2-3.3 (4H, m), 3.8-3.9 (4H, m), 6.7 (1H, m), 7.2-7.3 (3H, m), 7.4 (1H, s), 7.6-7.7 (3H, m), 8.2-8.3 (1H, s), 9.1 (1H, s)

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe yellow gum obtained
  3. customwas partitioned between Et2O and dilute HCl
  4. extractionThe aqueous layer was extracted with Et2O (1×10 mL)
  5. extractionextracted with DCM (3×10 mL)
  6. dry with materialThe DCM organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe brown gum obtained
  10. additionsilica (˜5 mL) added
  11. concentrationconcentrated under reduced pressure
  12. customThe solid obtained
  13. customto give a bright yellow solid
  14. customThis solid was triturated with Et2O
  15. filtrationfiltered
  16. washwashed with Et2O (3×5 mL) and pentane (3×5 mL)

Sources & evidence

ORD record
ord-2abcc9785edc4a869020461b51548ad2
Source dataset
uspto-grants-2011_09
Patent number
US08017619B2

Reaction notes

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