4-Methylmorpholine → HCID 86621008, compound

HRID 1715836Notes

Reaction equation

HRID 1715836 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21](O)=[O:22])[CH:19]=3)[CH2:14][CH2:13]2)(=[O:11])=[O:10])[CH:5]=[C:6]([CH3:8])[CH:7]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:55]([O:57][C:58](=[O:66])[CH2:59][C:60]1[N:61]=[C:62]([NH2:65])[S:63][CH:64]=1)[CH3:56]>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH2:55]([O:57][C:58](=[O:66])[CH2:59][C:60]1[N:61]=[C:62]([NH:65][C:21]([C:18]2[CH:19]=[C:20]3[C:15]([CH2:14][CH2:13][N:12]3[S:9]([C:4]3[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=3)(=[O:11])=[O:10])=[CH:16][CH:17]=2)=[O:22])[S:63][CH:64]=1)[CH3:56]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68435626HCID 68435626, compound

Product 1

HCID 86621008HCID 86621008, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(3,5-dimethyl-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carboxylic acid (0.20 g, 0.60 mmol) in dimethylformamide (1.00 mL) under argon was treated with N-methyl morpholine (0.31 g, 0.33 mL, 3.01 mmol), HATU (0.34 g, 0.90 mmol) and (2-amino-thiazol-4-yl)-acetic acid ethyl ester (0.17 g, 0.91 mmol). The mixture was stirred at room temperature for 30 min, then treated with 4-dimethylaminopyridine (0.07 g, 0.60 mmol). The mixture was warmed to 60° C. and stirred for 50 hours. After cooling to room temperature the mixture was partitioned between water and ethyl acetate. The organic phase was washed with brine, dried over magnesium sulphate and evaporated. The residue was purified via flash chromatography (heptane/ethyl acetate gradient) to yield (2-{[1-(3,5-dimethyl-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carbonyl]-amino}-thiazol-4-yl)-acetic acid ethyl ester as an off-white solid, 0.10 g (35%), MS (ISP): m/e=500.4 (M+H).

Workup

  1. temperatureThe mixture was warmed to 60° C.
  2. stirringstirred for 50 hours
  3. temperatureAfter cooling to room temperature the mixture
  4. customwas partitioned between water and ethyl acetate
  5. washThe organic phase was washed with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe residue was purified via flash chromatography (heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-4157b6d0362d4e6b9f0b2b30328efa06
Source dataset
uspto-grants-2010_09
Patent number
US07799933B2

Reaction notes

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