Hydrochloride methanol → HCID 58770700, compound

HRID 657262Notes

Reaction equation

HRID 657262 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.Cl.CO.[N+](C1C=CC(OC(=O)[NH:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][CH:55]([CH3:57])[CH3:56])=[CH:50][CH:49]=2)=CC=1)([O-])=O>>[CH:55]([O:54][C:51]1[CH:52]=[CH:53][C:48]([NH:47][C:6]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:21][CH:22]=4)[N:17]=[CH:16][N:15]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:49][CH:50]=1)([CH3:57])[CH3:56]

Participants

4

Reactant 3

HCID 21893726Hydrochloride methanolHCID 58769998(4-Isopropoxy-phenyl)-carbamic acid 4-nitrophenyl esterHCID 86609627HCID 86609627, compound

Product 1

HCID 58770700HCID 58770700, compoundYield 75%

Procedure

To 4-[7-(3-methanesulfonyloxy-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.1 mmol), prepared as described in Example 115, was added 3M HCl/MeOH (2 mL) and the mixture was stirred at rt for 2 h and then concentrated in vacuo and the residue was dissolved in a 1:1 mixture of DCM:MeOH, neutralized with excess Et3N and treated with (4-isopropoxy-phenyl)-carbamic acid 4-nitrophenyl ester (0.11 mmol), which was prepared as described in Example 1a. The mixture was stirred at rt overnight and then concentrated in vacuo and partitioned between water and DCM. DCM layer was drawn off, washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by Preparative TLC (silica gel; DCM:MeOH; 9.5:0.5) to obtain 40 mg (75%) of the title compound. 1H-NMR (300 MHz, CDCl3): 9.12 (s, 1H), 8.05 (d, 1H), 7.32-7.20 (m, 4H), 6.81 (d, 2H), 6.53 (s, 1H), 4.50-4.40 (m, 3H), 4.25 (t, 4H), 3.72-3.59 (m, 1H), 3.16-3.03 (m, 2H), 3.01 (s, 3H), 2.36-2.26 (m, 2H), 2.18-2.00 (m, 2H), 1.99-1.87 (m, 2H), 1.29 (d, 6H). LC/MS (ESI): 543.1 (MH)+.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue was dissolved in a 1:1 mixture of DCM
  3. customwas prepared
  4. stirringThe mixture was stirred at rt overnight
  5. concentrationconcentrated in vacuo
  6. custompartitioned between water and DCM
  7. washwashed with water thrice
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by Preparative TLC (silica gel; DCM:MeOH; 9.5:0.5)

Sources & evidence

ORD record
ord-a62f7c8273b74cee9a253ab31534da0b
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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