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

HRID 2111372Notes

Reaction equation

HRID 2111372 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([CH3:14])([CH3:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C=CC=CC=2[N+]([O-])=N1)C.C(N(C(C)C)C(C)C)C.[NH2:74][CH:75]1[CH2:80][CH2:79][N:78]([CH3:81])[CH2:77][CH2:76]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([CH3:13])([CH3:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:74][CH:75]5[CH2:80][CH2:79][N:78]([CH3:81])[CH2:77][CH2:76]5)=[O:27])=[CH:24][CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 581539364-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acidHCID 178484289HCID 178484289, compound

Product 1

HCID 250155384-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamideYield 49.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 0.0293 g (0.000072 mole) of 4-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid (I-50a) in 3 mL of dimethylformamide was added 0.0156 g (0.00012 mole) of 1-hydroxybenzotriazole, 0.043 g (0.00011 mole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate and 0.08 mL (0.0005 mole) of ethyldiisopropylamine. The mixture was stirred for 15 minutes and then 0.0129 g (0.00011 mole) of 4-amino-1-methylpiperidine was added. The mixture was stirred for an additional 2.5 hours and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with 1 M sodium hydroxide, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (98:2-85:15) to give 0.0181 g of 4-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-50).

Workup

  1. stirringThe mixture was stirred for an additional 2.5 hours
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed successively with 1 M sodium hydroxide, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with dichloromethane-methanol (98:2-85:15)

Sources & evidence

ORD record
ord-61333ab20fd04ac996183784fe23fe96
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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