Trifluoroacetic acid → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(piperidin-4-yl)benzamide

HRID 1676617

Reaction equation

HRID 1676617 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:45])[C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]3[N:24]=[CH:25][C:26]4[N:32]([CH3:33])[C:31](=[O:34])[C:30]([F:36])([F:35])[CH2:29][N:28]([CH:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[C:27]=4[N:42]=3)=[C:18]([O:43][CH3:44])[CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:37]1([N:28]2[CH2:29][C:30]([F:35])([F:36])[C:31](=[O:34])[N:32]([CH3:33])[C:26]3[CH:25]=[N:24][C:23]([NH:22][C:19]4[CH:20]=[CH:21][C:16]([C:15]([NH:14][CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)=[O:45])=[CH:17][C:18]=4[O:43][CH3:44])=[N:42][C:27]2=3)[CH2:38][CH2:39][CH2:40][CH2:41]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 44548769HCID 44548769, compound

Product 1

HCID 252530654-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(piperidin-4-yl)benzamideYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution 0.17 g (0.27 mmole) of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester (I-71) in 10 mL of dichloromethane was added 5 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 1 hour. After removal of the solvents under reduced pressure. Then dichloromethane and saturated sodium carbonate were added. The mixture was extracted with dichloromethane three times. The combined organic layers were washed three times with sodium carbonate, three times with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Dichloromethane and ether were added to the residue, followed by hexane to give a precipitate. The solid was collected by filtration, washing with hexane to give 0.125 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-piperidin-4-yl-benzamide (I-72) as a white solid.

Workup

  1. customAfter removal of the solvents under reduced pressure
  2. additionThen dichloromethane and saturated sodium carbonate were added
  3. extractionThe mixture was extracted with dichloromethane three times
  4. washThe combined organic layers were washed three times with sodium carbonate, three times with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionDichloromethane and ether were added to the residue
  9. customto give a precipitate
  10. filtrationThe solid was collected by filtration
  11. washwashing with hexane

Sources & evidence

ORD record
ord-bb5d6ff4a8ed485ba376f2947a705f3a
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Linked notes

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