Dimethylformamide → 2-[4-(4-Amino-quinazolin-7-ylmethyl)-3-oxo-piperazin-1-ylmethyl]-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 1432966Notes

Reaction equation

HRID 1432966 reaction equation
N12CCCN=C1CCCCC2.[C:12]([O:16][C:17](=[O:47])[NH:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1[C:25]#[C:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:44]=[C:43]3[C:38]([C:39]([NH2:45])=[N:40][CH:41]=[N:42]3)=[CH:37][CH:36]=2)[C:30](=[O:46])[CH2:29]1)([CH3:15])([CH3:14])[CH3:13].CN(C)C=O>CC#N.CCOC(C)=O.O>[C:12]([O:16][C:17]([N:18]1[C:19]2[CH:24]=[CH:23][N:22]=[CH:21][C:20]=2[CH:25]=[C:26]1[CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:44]=[C:43]3[C:38]([C:39]([NH2:45])=[N:40][CH:41]=[N:42]3)=[CH:37][CH:36]=2)[C:30](=[O:46])[CH2:29]1)=[O:47])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 69026971(3-{3-[4-(4-Amino-quinazolin-7-ylmethyl)-3-oxo-piperazin-1-yl]-prop-1-ynyl}-pyridin-4-yl)-carbamic acid tert-butyl ester

Product 1

HCID 538741592-[4-(4-Amino-quinazolin-7-ylmethyl)-3-oxo-piperazin-1-ylmethyl]-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl esterYield 85.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (37 mg, 0.24 mmol) is added to a suspension containing (3-{3-[4-(4-amino-quinazolin-7-ylmethyl)-3-oxo-piperazin-1-yl]-prop-1-ynyl}-pyridin-4-yl)-carbamic acid tert-butyl ester (59 mg, 0.12 mmol) in anhydrous CH3CN (5 mL) and the mixture is warmed to 50° C. Dimethylformamide (1 mL) is added to solubilize and the homogeneous solution is maintained for 5 h at 50° C. The reaction mixture is diluted with EtOAc (50 mL) and water (50 mL) and the layers are separated. The aqueous layer is extracted twice with EtOAc (25 mL) and the combined organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to provide 50 mg of the product as a crude solid which is used directly without further purification. 1H NMR (300 MHz, CDCl3) δ1.64 (s, 9H), 2.78 (m, 2H), 3.30 (m, 2H), 3.37 (s, 2H), 3.95 (s, 2H), 4.74 (s, 2H), 6.24 (br s, 2H), 6.63 (s, 1H), 7.40 (dd, J=8.5, 1.6 Hz, 1H), 7.64 (s, 1H), 7.81 (d, J=5.8 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.99 (s, 1H), 8.39 (d, J=5.8 Hz, 1H), 8.58 (s, 1H), 8.77 (s, 1H) ppm.

Workup

  1. temperaturethe homogeneous solution is maintained for 5 h at 50° C
  2. customthe layers are separated
  3. extractionThe aqueous layer is extracted twice with EtOAc (25 mL)
  4. washthe combined organic phase is washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dbdffd2b2b2b4d26bb9faf0cf6401de7
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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