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-(3-piperazin-1-yl-propyl)-benzamide

HRID 1676632Notes

Reaction equation

HRID 1676632 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH:17][C:18](=[O:48])[C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26]3[N:27]=[CH:28][C:29]4[N:35]([CH3:36])[C:34](=[O:37])[C:33]([F:39])([F:38])[CH2:32][N:31]([CH:40]5[CH2:44][CH2:43][CH2:42][CH2:41]5)[C:30]=4[N:45]=3)=[C:21]([O:46][CH3:47])[CH:20]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:40]1([N:31]2[CH2:32][C:33]([F:38])([F:39])[C:34](=[O:37])[N:35]([CH3:36])[C:29]3[CH:28]=[N:27][C:26]([NH:25][C:22]4[CH:23]=[CH:24][C:19]([C:18]([NH:17][CH2:16][CH2:15][CH2:14][N:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)=[O:48])=[CH:20][C:21]=4[O:46][CH3:47])=[N:45][C:30]2=3)[CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 580151564-{3-[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]-propyl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 580150464-(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-(3-piperazin-1-yl-propyl)-benzamideYield 80.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 0.0245 g (0.035 mmole) of 4-{3-[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]-propyl}-piperazine-1-carboxylic acid tert-butyl ester (I-94), 2.25 mL of dichloromethane and 0.25 mL of trifluoroacetic acid was stirred for 2 hours and then concentrated under reduced pressure. The residue was diluted with methanol and neutralized with 1.0 M sodium hydroxide at 0 degrees. The methanol solution was purified by reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 1:99-90:10) to give 0.0162 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-(3-piperazin-1-yl-propyl)-benzamide (I-95).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with methanol and neutralized with 1.0 M sodium hydroxide at 0 degrees
  3. customThe methanol solution was purified by reverse phase silica gel chromatography
  4. washeluting with acetonitrile-water (gradient, 1:99-90:10)

Sources & evidence

ORD record
ord-0b4b78f4b0b142cf91bae15619d3cbe4
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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