Hydrochloric Acid → HCID 59614403, compound

HRID 409458Notes

Reaction equation

HRID 409458 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9]CC)=[O:8])[CH2:3][CH2:2]1.[F:12][C:13]([F:55])([F:54])[C:14]1[CH:15]=[C:16]([CH:47]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:49]=1)[CH2:17][N:18]([C@H:31]1[CH2:35][C@@H:34]([CH2:36][O:37][CH3:38])[N:33]([C:39]2[C:44]([Cl:45])=[CH:43][N:42]=[C:41](Cl)[N:40]=2)[CH2:32]1)[C:19]1[N:24]=[CH:23][C:22]([C:25]2[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=2)=[CH:21][N:20]=1.[OH-].[Na+].Cl>C(O)(C)C>[F:52][C:50]([F:51])([F:53])[C:48]1[CH:47]=[C:16]([CH:15]=[C:14]([C:13]([F:12])([F:55])[F:54])[CH:49]=1)[CH2:17][N:18]([C:19]1[N:20]=[CH:21][C:22]([C:25]2[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=2)=[CH:23][N:24]=1)[C@@H:31]1[CH2:32][N:33]([C:39]2[C:44]([Cl:45])=[CH:43][N:42]=[C:41]([N:1]3[CH2:2][CH2:3][CH:4]([C:7]([OH:9])=[O:8])[CH2:5][CH2:6]3)[N:40]=2)[C@H:34]([CH2:36][O:37][CH3:38])[CH2:35]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 70770Ethyl 4-piperidinecarboxylateHCID 59614328HCID 59614328, compound

Product 1

HCID 59614403HCID 59614403, compoundYield 284.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 5 ml test tube for microwave reactor is charged with ethyl piperidine 4-carboxylate (202 mg, 1.28 mmol), (3,5-bis-trifluoromethyl-benzyl)-[(3S,5S)-1-(2,5-dichloro-pyrimidin-4-yl)-5-methoxymethyl-pyrrolidin-3-yl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (170 mg, 0.26 mmol) and isopropanol (1.5 ml). Then, the test tube is set into microwave reactor at 95 degree for 2 hours. After cooling to rt, reaction mixture is transferred into a 25 ml round-bottom flask and solvent is removed under reduced pressure. Then, into the flask is added 1N NaOH (1.28 ml, 1.28 mmol). The mixture is stirred for 1 hour, and pH is adjusted to 6-7 using 1.5 N HCl. The resulted solution is extracted with EtOAc and the organic layer is dried over MgSO4. The solvent is removed under reduced pressure, and the obtained residue is purified with reverse phase column to give 1-[4-((2S,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-methoxymethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid (78 mg, 0.74 mmol, 58% for 2 steps).

Workup

  1. customreaction mixture
  2. customis transferred into a 25 ml round-bottom flask
  3. customsolvent is removed under reduced pressure
  4. extractionThe resulted solution is extracted with EtOAc
  5. dry with materialthe organic layer is dried over MgSO4
  6. customThe solvent is removed under reduced pressure
  7. customthe obtained residue is purified with reverse phase column

Sources & evidence

ORD record
ord-578d7de958e841e99d5193ed40317afb
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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