2-Aminothiazole → HCID 58528874, compound

HRID 1431029Notes

Reaction equation

HRID 1431029 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:40]=[CH:41][C:42]=1[O:43][CH3:44])[CH2:5][O:6][P:7]([C:20]1[CH:39]=[CH:38][C:23]([O:24][C:25]2[CH:26]=[C:27]([CH:31]=[C:32]([O:34][CH:35]([CH3:37])[CH3:36])[CH:33]=2)[C:28]([OH:30])=O)=[CH:22][CH:21]=1)([O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([F:19])[CH:12]=1)=[O:8].[NH2:45][C:46]1[S:47][CH:48]=[CH:49][N:50]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O>[F:19][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[O:17][CH3:18])[CH2:10][O:9][P:7]([C:20]1[CH:21]=[CH:22][C:23]([O:24][C:25]2[CH:26]=[C:27]([C:28](=[O:30])[NH:45][C:46]3[S:47][CH:48]=[CH:49][N:50]=3)[CH:31]=[C:32]([O:34][CH:35]([CH3:36])[CH3:37])[CH:33]=2)=[CH:38][CH:39]=1)(=[O:8])[O:6][CH2:5][C:4]1[CH:40]=[CH:41][C:42]([O:43][CH3:44])=[C:2]([F:1])[CH:3]=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 86659569HCID 86659569, compound

Product 1

HCID 58528874HCID 58528874, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{4-[bis-(3-fluoro-4-methoxy-benzyloxy)-phosphoryl]-phenoxy}-5-isopropoxy-benzoic acid (350 mg, 0.557 mmol) in DMF (6 mL) was added 2-aminothiazole (70 mg, 0.696 mmol), HATU (265 mg, 0.696 mmol), and diisopropylethylamine (368 μL, 2.23 mmol). Stirred at rt for 16 h. The reaction mixture was diluted with EtOAc and washed with H2O (2×) and brine (2×). Dried with MgSO4, filtered, and concentrated. The residue was chromatographed on silica gel using an ethyl acetate-hexanes gradient to provide 164 mg (42%) of the title compound: 1H NMR (300 MHz, DMSO-d6): δ 12.68 (bs, 1H), 7.75 (dd, J=13, 9 Hz, 2H), 7.55 (d, J=4 Hz, 2H), 7.35 (s, 1H), 7.16 (m, 9H), 6.91 (s, 1H), 4.97 (dd, J=8, 2 Hz, 4H), 4.76 (m, 1H), 3.82 (s, 6H), 1.30 (d, J=6 Hz, 6H); LCMS m/z=711.6 [C35H33F2N2O8PS+H]+: Anal. Calcd. for (C35H33F2N2O8PS+1.2H2O): C, 57.41; H, 4.87; N, 3.83. Found: C, 57.06; H, 4.24; N, 3.91.

Workup

  1. washwashed with H2O (2×) and brine (2×)
  2. dry with materialDried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel using an ethyl acetate-hexanes gradient

Sources & evidence

ORD record
ord-56693a4e73694e268f901572fcea48b5
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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