4-Methylmorpholine → HCID 11605992, compound

HRID 854491Notes

Reaction equation

HRID 854491 reaction equation
[CH2:1]([N:3]([CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=2)[C:30]([OH:32])=O)[O:24][C:25]=1[CH3:26])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([OH:19])([C:15]([F:18])([F:17])[F:16])[C:11]([F:14])([F:13])[F:12])=[CH:6][CH:5]=1)[CH3:2].Cl.CN.[CH3:39][N:40]1CCOCC1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH4+].[Cl-]>CN(C=O)C.CCOCC>[CH2:1]([N:3]([CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=2)[C:30]([NH:40][CH3:39])=[O:32])[O:24][C:25]=1[CH3:26])[C:4]1[CH:5]=[CH:6][C:7]([C:10]([OH:19])([C:11]([F:14])([F:12])[F:13])[C:15]([F:18])([F:16])[F:17])=[CH:8][CH:9]=1)[CH3:2]

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 6364545Methylamine hydrochlorideHCID 11576980HCID 11576980, compound

Product 1

HCID 11605992HCID 11605992, compoundYield 82.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 22 mg (0.04 mmol) of 3-[4-({ethyl-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-amino}-methyl)-5-methyl-oxazol-2-yl]-benzoic acid (example 32) in 1 mL of DMF was treated with 9 mg (0.13 mmol) of methylamine hydrochloride and 0.03 mL (0.26 mmol) of 4-methylmorpholine and cooled to 0°. After addition of 12 mg (0.06 mmol) of EDCI and 1 mg (0.001 mmol) of HOBT the mixture was allowed to reach RT, stirred for 6 hours and distributed between Et2O and a saturated aqueous solution of NH4Cl. The combined organic phases were dried over Na2SO4 and evaporated. Column chromatography on silica gel with EtOAc gave 17 mg (75%) of 3-[4-({ethyl-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-amino}-methyl)-5-methyl-oxazol-2-yl]-N-methyl-benzamide, colorless gum, MS: 516 (MH+).

Workup

  1. temperaturecooled to 0°
  2. customto reach RT
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-ceae2998bae64baab443575d1306ead6
Source dataset
uspto-grants-2007_08
Patent number
US07259178B2

Reaction notes

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