Ammonium Chloride → Tert-butyl cis-2-(6-chloro-3-fluoro-5-(2-phenylpropan-2-ylaminocarbonyl)pyridin-2-ylamino)cyclohexylcarbamate

HRID 1620035Notes

Reaction equation

HRID 1620035 reaction equation
[C:1]([NH2:10])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[C:33]([O:37][C:38]([NH:40][C@H:41]1[CH2:46][CH2:45][CH2:44][CH2:43][C@H:42]1[NH:47][C:48]1[C:56]([F:57])=[CH:55][C:51]([C:52](O)=[O:53])=[C:50]([Cl:58])[N:49]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].[Cl-].[NH4+]>C(OCC)(=O)C.CN(C=O)C.O>[Cl:58][C:50]1[N:49]=[C:48]([NH:47][C@H:42]2[CH2:43][CH2:44][CH2:45][CH2:46][C@H:41]2[NH:40][C:38](=[O:39])[O:37][C:33]([CH3:36])([CH3:34])[CH3:35])[C:56]([F:57])=[CH:55][C:51]=1[C:52]([NH:10][C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2])=[O:53]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 68509CumylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866838426-(cis-2-(Tert-butoxycarbonylamino)cyclohexylamino)-2-chloro-5-fluoronicotinic acid

Product 1

HCID 86683841Tert-butyl cis-2-(6-chloro-3-fluoro-5-(2-phenylpropan-2-ylaminocarbonyl)pyridin-2-ylamino)cyclohexylcarbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cumylamine (1.97 ml), WSC.HCl (2.62 g), and HOBt.H2O (2.10 g) were added to a DMF (60 ml) solution containing 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-2-chloro-5-fluoronicotinic acid obtained in the 1st step, followed by stirring at room temperature for 4 hours. A saturated aqueous ammonium chloride solution and ethyl acetate were added to the reaction mixture. The organic layer was collected, washed with a saturated aqueous sodium hydrogen carbonate solution and then with saturated saline, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. Diisopropylether and hexane were added to the obtained residue, solid matter was collected by filtration, and a white solid of tert-butyl cis-2-(6-chloro-3-fluoro-5-(2-phenylpropan-2-ylaminocarbonyl)pyridin-2-ylamino)cyclohexylcarbamate (4.41 g) was thus obtained.

Workup

  1. customobtained in the 1st step
  2. customThe organic layer was collected
  3. washwashed with a saturated aqueous sodium hydrogen carbonate solution
  4. dry with materialwith saturated saline, and dried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. additionDiisopropylether and hexane were added to the obtained residue, solid matter
  7. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-fa21bf6621e946d38a9d8249b8271fb6
Source dataset
uspto-grants-2014_07
Patent number
US08772320B2

Reaction notes

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