3-Aminophenyl dimethylcarbamate → 3-(4-amino-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate

HRID 2098383Notes

Reaction equation

HRID 2098383 reaction equation
C(OC(NC1(C(=O)[NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31](=[O:35])[N:32]([CH3:34])[CH3:33])[CH:25]=2)CCN(C(OC(C)(C)C)=O)CC1)=O)(C)(C)C.CC(OC([NH:44][C:45]1([C:58]([OH:60])=O)[CH2:50][CH2:49][N:48]([C:51](OC(C)(C)C)=O)[CH2:47][CH2:46]1)=O)(C)C.CN(C(O[N:69]1N=[N:76][C:71]2[CH:72]=[CH:73][CH:74]=[N:75][C:70]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:85](N(CC)C(C)C)(C)C.CN(C)C(=O)OC1C=CC=C(N)C=1>C(OC(C)C)(=O)C.CCOC(C)=O>[CH3:34][N:32]([CH3:33])[C:31](=[O:35])[O:30][C:26]1[CH:27]=[CH:28][CH:29]=[C:24]([NH:23][C:58]([C:45]2([NH2:44])[CH2:46][CH2:47][N:48]([C:51]3[C:73]4[C:72]([CH3:85])=[CH:71][NH:76][C:74]=4[N:75]=[CH:70][N:69]=3)[CH2:49][CH2:50]2)=[O:60])[CH:25]=1

Participants

8

Reactant 5

HCID 298773-Aminophenyl dimethylcarbamateHCID 81531DiisopropylethylamineHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68992221Tert-butyl 4-(tert-butoxycarbonylamino)-4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)piperidine-1-carboxylate

Product 1

HCID 579202093-(4-amino-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamateYield 45%

Reagents, catalysts & solvents 2

HCID 7915Isopropyl AcetateSolventHCID 8857Ethyl AcetateSolvent

Procedure

Preparation of tert-butyl 4-(tert-butoxycarbonylamino)-4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)piperidine-1-carboxylate. N-Boc-amino-(4-N-Boc-piperidinyl) carboxylic acid (0.114 g, 0.33 mmol), HATU (0.151 g, 0.40 mmol) and N,N-diisopropylethylamine (128 mg, 1.0 mmol) were combined in isopropyl acetate (2.3 mL) and stirred at room temperature for 15 minutes. 3-aminophenyl dimethylcarbamate (0.072 g, 0.40 mmol) was added, and the mixture heated at 80° C. for 1.5 hours. The reaction mixture was allowed to cool, diluted with EtOAc, washed with 2 N Na2CO3, 1 N HCl, and brine, and then dried over MgSO4 and concentrated. Purification by silica gel chromatography (60% EtOAc/hexanes) gave the title compound (0.075 g, 45%) as a white solid. MS (ES+) [M+NH4]+=524.

Workup

  1. temperaturethe mixture heated at 80° C. for 1.5 hours
  2. temperatureto cool
  3. washwashed with 2 N Na2CO3, 1 N HCl, and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-be79bfa656cc463fbc13b9df02fd7ad7
Source dataset
uspto-grants-2013_05
Patent number
US08450332B2

Reaction notes

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