Water → HCID 42635493, compound

HRID 409437Notes

Reaction equation

HRID 409437 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]([CH:20]1[CH2:24][CH: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.[CH2:36]([O:38][C:39](C1OC(Cl)=NC=1)=[O:40])[CH3:37].[CH:47](N(CC)C(C)C)(C)C.O.[CH3:57][N:58]([CH:60]=[O:61])C>>[CH2:36]([O:38][C:39]([C:57]1[N:58]=[C:60]([N:22]2[CH2:21][C@@H:20]([N:7]([CH2:6][C:5]3[CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=[C:3]([C:2]([F:34])([F:1])[F:35])[CH:4]=3)[C:8]3[N:9]=[CH:10][C:11]([C:14]4[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=4)=[CH:12][N:13]=3)[CH2:24][C@H:23]2[CH2:25][CH3:26])[O:61][CH:47]=1)=[O:40])[CH3:37]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 26369855Ethyl 2-chloro-1,3-oxazole-5-carboxylateHCID 72338961[3,5-bis(trifluoromethyl)benzyl]-(5-ethyl-pyrrolidin-3-yl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine

Product 1

HCID 42635493HCID 42635493, compoundYield 46%

Conditions

Temperature
120 °C

Procedure

A solution of [3,5-bis(trifluoromethyl)benzyl]-(5-ethyl-pyrrolidin-3-yl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (0.025 mmol, 12.5 mg), 2-chloro-oxazole-5-carboxylic acid ethyl ester (0.03 mmol, 5 mg) and N, N-diisopropylethylamine (0.03 mmol, 5 uL) in DMF (0.1 mL) is allowed to warm to 120° C. and stirred for 3 hours. The mixture is cooled to room temperature, then added with water. The mixture is extracted with CH2Cl2. The combined organic layer is dried over Na2SO4, filtrated, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give 2-((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-oxazole-4-carboxylic acid ethyl ester (7.4 mg, 46%); ESI-MS m/z: 638 [M+1]+, Retention time 2.20 min (condition A).

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. extractionThe mixture is extracted with CH2Cl2
  3. dry with materialThe combined organic layer is dried over Na2SO4
  4. filtrationfiltrated
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-4f548b4a00c142b29036c3b1ac6f9060
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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