Trifluoroacetic acid → (R)-N-(1-(cyclopropylmethyl)-2-oxoazepan-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide

HRID 1271497Notes

Reaction equation

HRID 1271497 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([CH2:11][N:12]2[CH2:18][CH2:17][CH2:16][CH2:15][C@@H:14]([NH:19][C:20](=[O:26])OC(C)(C)C)[C:13]2=[O:27])[CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.[O:37]=[C:38]1[N:47]([CH:48]2[CH2:53][CH2:52][N:51](C(Cl)=O)[CH2:50][CH2:49]2)[CH2:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[NH:39]1>ClCCl.ClCCCl>[CH:8]1([CH2:11][N:12]2[CH2:18][CH2:17][CH2:16][CH2:15][C@@H:14]([NH:19][C:20]([N:51]3[CH2:50][CH2:49][CH:48]([N:47]4[CH2:46][C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[NH:39][C:38]4=[O:37])[CH2:53][CH2:52]3)=[O:26])[C:13]2=[O:27])[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 183211084-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carbonyl chlorideHCID 58695830tert-Butyl (3R)-1-(cyclopropylmethyl)-2-oxoazepan-3-ylcarbamate

Product 1

HCID 11224441(R)-N-(1-(cyclopropylmethyl)-2-oxoazepan-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (5 mL) was added to a solution of tert-butyl (3R)-1-(cyclopropylmethyl)-2-oxoazepan-3-ylcarbamate (257 mg, 0.91 mmol) in dichloromethane (10 mL). After 1 h, the mixture was concentrated and azeotroped with dichloromethane (3×) to give the crude amine. Diisopropylethylamine (0.070 mL, 0.40 mmol) was added to a solution of the crude amine (39 mg, 0.13 mmol) and 4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carbonyl chloride (39 mg, 0.13 mmol) in 1,2-dichloroethane (2 mL) and the mixture was heated to reflux. After 1 h, the reaction was allowed to cool to ambient temperature. Purification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane) gave the title compound (32 mg). MS 440 (M+1).

Workup

  1. concentrationthe mixture was concentrated
  2. customazeotroped with dichloromethane (3×)
  3. customto give the crude amine
  4. temperaturethe mixture was heated to reflux
  5. waitAfter 1 h
  6. customPurification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-0618bcc0c6284b3abe73c7cb36a6c385
Source dataset
uspto-grants-2007_04
Patent number
US07205292B2

Reaction notes

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