2-Aminothiazole → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-1,3-thiazol-2-ylbenzamide

HRID 1990224Notes

Reaction equation

HRID 1990224 reaction equation
CCN(C(C)C)C(C)C.[N:10]1([C:14]([C:16]2[CH:17]=[C:18]([Cl:38])[C:19]([O:22][C:23]3[CH:24]=[C:25]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:31]=3)[C:26](O)=[O:27])=[N:20][CH:21]=2)=[O:15])[CH2:13][CH2:12][CH2:11]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:63][C:64]1[S:65][CH:66]=[CH:67][N:68]=1>CN(C=O)C.O>[N:10]1([C:14]([C:16]2[CH:17]=[C:18]([Cl:38])[C:19]([O:22][C:23]3[CH:24]=[C:25]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:31]=3)[C:26]([NH:63][C:64]3[S:65][CH:66]=[CH:67][N:68]=3)=[O:27])=[N:20][CH:21]=2)=[O:15])[CH2:11][CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 536296673-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid

Product 1

HCID 160398663-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-1,3-thiazol-2-ylbenzamideYield 37.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.129 mL) was added to a suspension of 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid (168 mg), HATU (190 mg) and 2-aminothiazole (40 mg) in DMF (2 mL) and the mixture stirred at RT for 16 hours. Water (30 mL) was added and the mixture extracted with ethyl acetate (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with 50-100% ethyl acetate in isohexane, to give the desired compound (75 mg).

Workup

  1. extractionthe mixture extracted with ethyl acetate (3×20 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to a residue which
  5. customwas chromatographed on silica
  6. washeluting with 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-725774acb0d5489e9adbc67644b803ac
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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