Trifluoroacetic acid → 4-[7-(3-Methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

HRID 657242Notes

Reaction equation

HRID 657242 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][NH: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.C(O)(C(F)(F)F)=O.[Al].Cl.[N+](C1C=CC(OC(=O)[NH:53][C:54]2[CH:59]=[CH:58][C:57]([N:60]3[CH2:65][CH2:64][O:63][CH2:62][CH2:61]3)=[CH:56][CH:55]=2)=CC=1)([O-])=O>>[N:60]1([C:57]2[CH:56]=[CH:55][C:54]([NH:53][C:6]([N:8]3[CH2:9][CH2:10][CH:11]([C:14]4[C:23]5[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:21][CH:22]=5)[N:17]=[CH:16][N:15]=4)[CH2:12][CH2:13]3)=[O:7])=[CH:59][CH:58]=2)[CH2:61][CH2:62][O:63][CH2:64][CH2:65]1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5359268AluminumHCID 595516844-[7-(3-Methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl esterHCID 68947764(4-Morpholin-4-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride

Product 1

HCID 587708164-[7-(3-Methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-morpholin-4-yl-phenyl)-amideYield 39%

Conditions

Temperature
80 °C

Procedure

4-[7-(3-methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (7.4 mg, 16 μmol), as prepared in Example 65c, and TFA (100 μL, 1.35 mmol) was capped tightly and stirred at 100° C. (aluminum block) for 5 min. The reaction was then concentrated, and pyridine (100 μL) was added to give a homogeneous solution. (4-Morpholin-4-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride (7.5 mg, 20 μmol) was then added in one portion at rt, and the solution was stirred at 80° C. for 10 min, then at rt overnight. The reaction was then concentrated and subjected to silica flash chromatography (4:3→3:5 DCM/acetone) to afford the title compound as an off-white semisolid (3.5 mg, 39%). 1H-NMR (400 MHz, 95:5 v/v CDCl3:CD3OD) δ 9.10 (s, 1H), 8.09 (d, 1H), 7.33-7.25 (m, 4H), 6.89 (m, 2H), 4.27 (m, 4H), 3.87 (m, 4H), 3.70 (m, 1H), 3.38 (t, 2H), 3.17-3.07 (m, 6H), 2.96 (s, 3H), 2.20-2.05 (m, 4H), 2.01-1.92 (m, 2H). LC/MS (ESI): calcd mass 568.2, found 569.1 (MH)+.

Workup

  1. customwas capped tightly
  2. concentrationThe reaction was then concentrated
  3. additionpyridine (100 μL) was added
  4. customto give a homogeneous solution
  5. customat rt
  6. customovernight
  7. concentrationThe reaction was then concentrated

Sources & evidence

ORD record
ord-5cc746c6d3f046c48041e60eb2d791e3
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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