Trifluoroacetic acid → HCID 42634257, compound

HRID 409431Notes

Reaction equation

HRID 409431 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:26][C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([F:40])([F:39])[F:38])[CH:28]=2)[C:14]2[N:19]=[CH:18][C:17]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:41][CH3:42])=[O:7])(C)([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N(CC)C(C)C)(C)C.ClC(OC(C)C)=O>ClCCl.O>[CH:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:26][C:27]2[CH:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:30]=[C:29]([C:37]([F:38])([F:39])[F:40])[CH:28]=2)[C:14]2[N:15]=[CH:16][C:17]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)=[CH:18][N:19]=2)[CH2:10][C@H:9]1[CH2:41][CH3:42])=[O:7])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 42633526HCID 42633526, compound

Product 1

HCID 42634257HCID 42634257, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.200 mmol; 120 mg) in dichloromethane (2.0 mL) is added trifluoroacetic acid (0.7 mL). The mixture is stirred for 1 hour, and then concentrated under reduced pressure. To a mixture of the obtained residue and N,N-diisopropylethylamine (1.6 mmol; 207 mg) is added isopropyl chloroformate (0.4 mmol; 49 mg). The mixture is stirred for 1 hour at room temperature, and then diluted with water and dichloromethane. The organic layer is separated to 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-pyrrolidine-1-carboxylic acid isopropyl ester (51 mg, 73%); ESI-MS m/z: 599 [M+1]+, Retention time 2.15 min (condition A).

Workup

  1. concentrationconcentrated under reduced pressure
  2. stirringThe mixture is stirred for 1 hour at room temperature
  3. customThe organic layer is separated
  4. concentrationto concentrated under reduced pressure
  5. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-a19fc1f9c551463daff891f691914120
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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