Pyridine → HCID 42635494, compound

HRID 409438Notes

Reaction equation

HRID 409438 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C@H:20]1[CH2:24][C@@H:23]([CH2:25][CH3:26])[NH:22][CH2:21]1)[C:8]1[N:13]=[CH:12][C:11]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[CH:10][N:9]=1.ClC(Cl)(O[C:40](=[O:46])OC(Cl)(Cl)Cl)Cl.[N:48]1[CH:53]=[CH:52][CH:51]=[CH:50]C=1.[NH4+].[Cl-].N1CCCC1>C(Cl)Cl.CCOC(C)=O>[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C:8]1[N:9]=[CH:10][C:11]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[CH:12][N:13]=1)[C@@H:20]1[CH2:21][N:22]([C:40]([N:48]2[CH2:50][CH2:51][CH2:52][CH2:53]2)=[O:46])[C@H:23]([CH2:25][CH3:26])[CH2:24]1

Participants

8

Reactant 5

HCID 1049PyridineHCID 25517Ammonium Chloride2×HCID 31268PyrrolidineHCID 94429TriphosgeneHCID 59614335HCID 59614335, compound

Product 1

HCID 42635494HCID 42635494, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

[3,5-Bis(trifluoromethyl)benzyl]-((3S,5R)-5-ethyl-pyrrolidin-3-yl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (84 mg, 0.17 mmol) and triphosgene (71 mg, 0.24 mmol) are dissolved in CH2Cl2 (2 mL). The reaction mixture is stirred at room temperature for 1 hour after addition of pyridine (15 mg, 0.19 mmol). Saturated aqueous NH4Cl and EtOAc are added, then extracted with EtOAc. The combined organic layer is dried over Na2SO4 then concentrated under reduced pressure. The resulting residue is dissolved in CH2Cl2 (1.5 mL) and then pyrrolidine (60 mg, 0.85 mmol) is added. The reaction mixture is stirred at room temperature for 12 hours. Saturated aqueous NH4Cl and CH2Cl2 are added, then extracted with CH2Cl2. The combined organic layer is dried over MgSO4, then concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give ((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-pyrrolidin-1-yl-methanone (45 mg, 36%); ESI-MS m/z: 596 [M+1]+, Retention time 4.52 min (condition B).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic layer is dried over Na2SO4
  3. concentrationthen concentrated under reduced pressure
  4. dissolutionThe resulting residue is dissolved in CH2Cl2 (1.5 mL)
  5. stirringThe reaction mixture is stirred at room temperature for 12 hours
  6. extractionextracted with CH2Cl2
  7. dry with materialThe combined organic layer is dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-9d0a8ac6cefa438d93bd5cb868388600
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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