Triethylamine → HCID 68693367, compound

HRID 657260Notes

Reaction equation

HRID 657260 reaction equation
C(O)CCO.[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:29][CH2:30][CH2:31][CH2:32][OH:33])=[CH:26][CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CCN(CC)CC.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>C(Cl)Cl>[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:29][CH2:30][CH2:31][CH2:32][OH:33])=[CH:26][CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:29][CH2:30][CH2:31][CH2:32][O:33][S:42]([CH3:41])(=[O:44])=[O:43])=[CH:26][CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 104421,3-PropanediolHCID 31297Methanesulfonyl chlorideHCID 68693367HCID 68693367, compound

Product 2

HCID 68693367HCID 68693367, compoundHCID 86609627HCID 86609627, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[7-(-Hydroxy-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester was prepared as described in Example 33 using propane-1,3-diol in place of 3-hydroxypropylpiperidine. To a solution of 4-[7-(-hydroxy-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.3 mmol) in anhydrous DCM, was added Et3N (0.6 mmol) and methanesulfonyl chloride (0.6 mmol) and the mixture was stirred at rt for 2 h. It was then washed with water (3×), dried over anhydrous MgSO4, filtered and concentrated in vacuo to obtain 4-[7-(3-methanesulfonyloxy-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester. This (0.05 mmol) was dissolved in anhydrous dioxane together with 1-ethyl-piperazine (0.1 mmol) and the mixture was stirred at 100° C. overnight and then concentrated in vacuo, then diluted with water and extracted with DCM. The DCM extract was washed with water (3×), dried over anhydrous MgSO4, filtered and concentrated in vacuo. To this was added 3M HCl/MeOH (1 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-morpholin-4-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride (0.06 mmol), which was prepared as described in Example 66a. 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:NH4OH; 90:9:1) to obtain 9.4 mg (32%) of the title compound. 1H-NMR (300 MHz, CDCl3): 9.13 (s, 1H), 8.04 (d, 1H), 7.35-7.22 (m, 4H), 6.88 (d, 2H), 6.33 (s, 1H), 4.32-4.15 (m, 4H), 3.89-3.81 (m, 4H), 3.74-3.60 (m, 1H), 3.20-3.04 (m, 7H), 2.66-2.35 (m, 12H), 2.22-1.88 (m, 5H), 1.10 (t, 3H). LC/MS (ESI): 588.1 (MH)+.

Workup

  1. washIt was then washed with water (3×)
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-31333ad282594efabc87114bb39f5db0
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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