Hydrochloric Acid → HCID 66876208, compound

HRID 1917807Notes

Reaction equation

HRID 1917807 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-2d18821af0b84d1ea27e16b39c558d1d
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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