Triethylamine → tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

HRID 1623335Notes

Reaction equation

HRID 1623335 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C@@H:27]([CH3:39])[CH2:26]1.[NH2:40][C@@H:41]1[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:43]([CH3:55])[CH2:42]1.C(N(CC)CC)C>CS(C)=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[C@@H:27]([CH3:39])[CH2:26]2)=[N:6][CH:7]=1.[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:40][C@@H:41]2[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[C@H:43]([CH3:55])[CH2:42]2)=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 58127193HCID 58127193, compoundHCID 86650623tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate

Product 1

HCID 86650625tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Intermediate B (preparation of intermediate B is described in the intermediate session which is in front of the Examples) (25 mg, 0.075 mmol), tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate/tert-butyl(1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate (25.8 mg, 0.113 mmol), triethylamine (28 μl, 0.201 mmol) in DMSO (0.25 mL) was heated at 100° C. for 3 days. The mixture was allowed to cool to ambient temperature and diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 solution (10 mL). The separated aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered off and concentrated in vacuo providing crude tert-butyl (1S,2S,4S)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate/tert-butyl (1R,2R,4R)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate, which was directly used in the next step without further purification.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionThe separated aqueous layer was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1ac8c8ddc6d34bf98e19e0851fe482f1
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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