Hydrochloric Acid → HCID 42635308, compound

HRID 409436Notes

Reaction equation

HRID 409436 reaction equation
[C:1]([C:4]([CH3:45])([CH3:44])[CH2:5][O:6][C:7]([N:9]1[CH2:13][C@@H:12]([N:14]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:15]2[N:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)=[CH:17][N:16]=2)[CH2:11][C@H:10]1[CH2:42][CH3:43])=[O:8])(O)=[O:2].[Cl-].[NH4+].Cl.C1C=[N:53]C2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[C:1]([C:4]([CH3:45])([CH3:44])[CH2:5][O:6][C:7]([N:9]1[CH2:13][C@@H:12]([N:14]([CH2:27][C:28]2[CH:29]=[C:30]([C:38]([F:41])([F:39])[F:40])[CH:31]=[C:32]([C:34]([F:36])([F:35])[F:37])[CH:33]=2)[C:15]2[N:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)=[CH:17][N:16]=2)[CH2:11][C@H:10]1[CH2:42][CH3:43])=[O:8])(=[O:2])[NH2:53]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 181649HOAtHCID 42633528HCID 42633528, compound

Product 1

HCID 42635308HCID 42635308, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 2-carboxy-2-methylpropyl ester (0.016 mmol; 10 mg), ammonium chloride (0.032 mmol; 1.7 mg), WSCD hydrochloride (0.032 mmol; 7.3 mg), HOAt (0.032 mmol; 4.4 mg) in DMF (0.4 ml) is added triethylamine (0.080 mol; 8.1 mg) at room temperature. The reaction mixture is stirred for 18.5 hours at the same temperature, and then quenched with water. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, concentrated under reduced pressure. The obtained residue is purified by preparative thin layer chromatography on silica gel (eluent: dichloromethane/MeOH) 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 2-carbamoyl-2-methyl-propyl ester (4.1 mg, 40%); ESI-MS m/z: 642 [M+1]+, Retention time 2.04 min (condition A).

Workup

  1. customquenched with water
  2. extractionThe product is extracted three times with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by preparative thin layer chromatography on silica gel (eluent: dichloromethane/MeOH)

Sources & evidence

ORD record
ord-21e309197aff4368b4773398aa2bd3ba
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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