Diisopropylethylamine → Methyl 1-{[(3-chloro-2'-{4-chloro-3-[3-(dimethylamino)propoxy]-phenyl}-5-methyl-2,3'-bipyridin-6'-yl)carbonyl]amino}cyclohexane-carboxylate hydrochloride

HRID 1259531Notes

Reaction equation

HRID 1259531 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[C:10]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[CH:19]=3)=[N:11][C:12]([C:15](O)=[O:16])=[CH:13][CH:14]=2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CCN(C(C)C)C(C)C.Cl.[NH2:42][C:43]1([C:49]([O:51][CH3:52])=[O:50])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(#N)C>[ClH:1].[Cl:1][C:2]1[C:3]([C:9]2[C:10]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:30])[CH3:31])[CH:19]=3)=[N:11][C:12]([C:15]([NH:42][C:43]3([C:49]([O:51][CH3:52])=[O:50])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)=[O:16])=[CH:13][CH:14]=2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 22645079Methyl 1-aminocyclohexane-1-carboxylate hydrochlorideHCID 668409423-Chloro-2'-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-methyl-2,3'-bipyridine-6'-carboxylic acid

Product 1

HCID 66840590Methyl 1-{[(3-chloro-2'-{4-chloro-3-[3-(dimethylamino)propoxy]-phenyl}-5-methyl-2,3'-bipyridin-6'-yl)carbonyl]amino}cyclohexane-carboxylate hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 134 mg (0.29 mmol) of 3-chloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-methyl-2,3′-bipyridine-6′-carboxylic acid in 5 mL of anhydrous acetonitrile are successively added 0.18 mL (1.02 mmol) of DIEA and 56 mg (0.29 mmol) of methyl 1-aminocyclo-hexanecarboxylate hydrochloride. The mixture is cooled to 0° C. and 112 mg (0.35 mmol) of TBTU are added. After stirring for 18 hours between 0 and 10° C., the reaction medium is concentrated under reduced pressure and then taken up in 20 mL of a 1/1 EtOAc/ether mixture. After washing with 10 mL of water and 10 mL of saturated aqueous NaHCO3 solution, the organic phase is dried over Na2SO4 and concentrated under reduced pressure. 0.2 mL (0.1 mmol) of a 2N solution of HCl in ether and then 20 mL of anhydrous ether are added to the residue, taken up in 5 mL of DCM, which allows precipitation of 139 mg of methyl 1-{[(3-chloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-methyl-2,3′-bipyridin-6′-yl)carbonyl]amino}cyclohexanecarboxylate hydrochloride in the form of a white powder.

Workup

  1. concentrationthe reaction medium is concentrated under reduced pressure
  2. washAfter washing with 10 mL of water and 10 mL of saturated aqueous NaHCO3 solution
  3. dry with materialthe organic phase is dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. addition0.2 mL (0.1 mmol) of a 2N solution of HCl in ether and then 20 mL of anhydrous ether are added to the residue
  6. customprecipitation of 139 mg of methyl 1-{[(3-chloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-methyl-2,3′-bipyridin-6′-yl)carbonyl]amino}cyclohexanecarboxylate hydrochloride in the form of a white powder

Sources & evidence

ORD record
ord-3857948397c44bca9a70203ec62efdf2
Source dataset
uspto-grants-2013_06
Patent number
US08466292B2

Reaction notes

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