Hydrochloric Acid → HCID 66876208, compound

HRID 871408Notes

Reaction equation

HRID 871408 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:43])[NH:12][C:13]2[CH:14]=[C:15]([CH:40]=[CH:41][CH:42]=2)[O:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][CH2:30][CH:31]4[CH2:36][CH2:35][N:34](C([O-])=O)[CH2:33][CH2:32]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl>ClCCl>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:12][C:13]2[CH:42]=[CH:41][CH:40]=[C:15]([O:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][CH2:30][CH:31]5[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]5)=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:14]=2)=[O:43])[O:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86653513HCID 86653513, compound

Product 1

HCID 66876208HCID 66876208, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-((4-(3-(3-(3-tert-butylisoxazol-5-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate (49 mg, 0.062 mmol) in dichloromethane (0.31 mL) was added hydrochloric acid (0.31 mL, 4M in dioxane) and the mixture stirred at room temperature for 30 minutes. The solid was filtered off, dissolved in methanol and concentrated under reduced pressure. The residue was taken in ethyl acetate and a saturated solution of sodium bicarbonate was added until the solution became basic. The solid was filtered off, washed thoroughly with water and dried to afford 1-(3-tert-butylisoxazol-5-yl)-3-(3-(6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-yloxy)phenyl)urea as a white solid (23.31 mg, 69%). 1H NMR (300 MHz, DMSO-d6) δ 10.10 (bs, 1H), 9.65 (bs, 1H), 8.56 (s, 1H), 7.61-7.21 (m, 5H), 6.95 (d, 1H), 6.56 (s, 1H), 4.25-3.90 (m, 6H), 3.00 (d, 2H), 2.45 (d, 2H), 2.20-1.79 (m, 1H), 1.78-1.51 (m, 4H), 1.25 (s, 9H); LC-MS (ESI) m/z 547 (M+H)+.

Workup

  1. filtrationThe solid was filtered off
  2. dissolutiondissolved in methanol
  3. concentrationconcentrated under reduced pressure
  4. additiona saturated solution of sodium bicarbonate was added until the solution
  5. filtrationThe solid was filtered off
  6. washwashed thoroughly with water
  7. customdried

Sources & evidence

ORD record
ord-c0d88ea9fb71443fa8f9a2b4404710e9
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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