Triethylamine → HCID 86671253, compound

HRID 1952554Notes

Reaction equation

HRID 1952554 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH2:11])=[N:8][C:7]=1[CH3:12])=[O:5])[CH3:2].C(N(CC)CC)C.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[N:26]1[C:34]2[C:29](=[C:30]([CH2:35][C:36](O)=[O:37])[CH:31]=[CH:32][CH:33]=2)[CH:28]=[N:27]1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(OCC)(=O)C>C1COCC1.O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:36](=[O:37])[CH2:35][C:30]2[CH:31]=[CH:32][CH:33]=[C:34]3[C:29]=2[CH:28]=[N:27][N:26]3[CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)=[N:8][C:7]=1[CH3:12])=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 343747Ethyl 2-amino-4-methylthiazole-5-carboxylateHCID 68226631[1-(Tetrahydro-pyran-2-yl)-1H-indazol-4-yl]acetic acid

Product 1

HCID 86671253HCID 86671253, compoundYield 73.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 2-Amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (1.74 g, 9.343 mmol) and triethylamine (5.2 mL, 37.31 mol) in anhydrous THF (40 mL) was heated to 60° C. and [1-(Tetrahydro-pyran-2-yl)-1H-indazol-4-yl]acetic acid (1.85 g, 7.107 mmol) in anhydrous THF (20 mL) was added followed by the addition of 1-propanephosphonic acid cyclic anhydride, 50 wt. % solution in ethyl acetate (5.2 mL, 8.735 mmol) over 1 min. The reaction mixture was heated at 60° C. for 40 min, cooled, diluted with water (150 mL) and extracted with ethyl acetate (3×150 mL). The organic layers were combined, washed with 1/1 aqueous 2N HCl/brine (100 mL), brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (33% EtOAc in hexanes) to give 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid ethyl ester (2.23 g, 73%) as a yellow foam. MS m/e 429.5 (M+H+).

Workup

  1. temperaturecooled
  2. extractionextracted with ethyl acetate (3×150 mL)
  3. washwashed with 1/1 aqueous 2N HCl/brine (100 mL), brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude compound was purified by flash chromatography (33% EtOAc in hexanes)

Sources & evidence

ORD record
ord-51c62568553948a0aa7aa6e65b5cfe59
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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