Piperidine → 2-[4-(4-Amino-piperidine-1-carbonyl)-phenylamino]-9-cyclobutyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 1676557Notes

Reaction equation

HRID 1676557 reaction equation
C1C2C(COC(=O)[NH:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:51])[C:25]4[CH:30]=[CH:29][C:28]([NH:31][C:32]5[N:33]=[CH:34][C:35]6[N:41]([CH3:42])[C:40](=[O:43])[C:39]([F:45])([F:44])[CH2:38][N:37]([CH:46]7[CH2:49][CH2:48][CH2:47]7)[C:36]=6[N:50]=5)=[CH:27][CH:26]=4)[CH2:20][CH2:19]3)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>ClCCl>[NH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]3[N:33]=[CH:34][C:35]4[N:41]([CH3:42])[C:40](=[O:43])[C:39]([F:44])([F:45])[CH2:38][N:37]([CH:46]5[CH2:47][CH2:48][CH2:49]5)[C:36]=4[N:50]=3)=[CH:27][CH:26]=2)=[O:51])[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 67354975{1-[4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 445473552-[4-(4-Amino-piperidine-1-carbonyl)-phenylamino]-9-cyclobutyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 25.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 0.220 g (0.31 mmole) of {1-[4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoyl]-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester, 1 mL of piperidine and 5 mL of dichloromethane was stirred for 1 hour and then concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol-ammonium hydroxide (92:8:0.3) to give 0.038 g of 2-[4-(4-amino-piperidine-1-carbonyl)-phenylamino]-9-cyclobutyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (I-15).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by silica gel chromatography
  3. washeluting with dichloromethane-methanol-ammonium hydroxide (92:8:0.3)

Sources & evidence

ORD record
ord-60cfa6c179c245fcae7d1c823d1b1328
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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