Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-amino-5,6-dichloro-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamide

HRID 2407810Notes

Reaction equation

HRID 2407810 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([OH:12])=O)[CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.Cl.Cl.[N:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[C:49]1[S:50][C:51]([CH2:54][N:55]2[CH2:60][CH2:59][CH:58]([CH2:61][NH2:62])[CH2:57][CH2:56]2)=[CH:52][N:53]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([NH:62][CH2:61][CH:58]2[CH2:59][CH2:60][N:55]([CH2:54][C:51]3[S:50][C:49]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][N:43]=4)=[N:53][CH:52]=3)[CH2:56][CH2:57]2)=[O:12])[CH:3]=1

Participants

8

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 585040704-Amino-5,6-dichloropicolinic AcidHCID 66989375(1-((2-(Pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methanamine Trihydrochloride

Product 1

HCID 585039374-amino-5,6-dichloro-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamideYield 73.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

The compound prepared in Example 406 (0.533 g), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (2.0098 g), the compound prepared in Example 214 (1.3315 g) and triethyl amine were suspended in dimethyl formamide (40 mL) and stirred at room temperature overnight. The reaction mixture was poured onto saturated aqueous sodium bicarbonate and ethyl acetate. The organics were washed with brine, dried over with magnesium sulfate and concentrated under reduced pressure to afford the crude material. The crude material was purified by flash column chromatography (eluant gradient elution 1-5% (9:1=methanol:ammonium hydroxide)/ethyl acetate) to furnish the title compound (0.902 g), possessing the following physical data.

Workup

  1. washThe organics were washed with brine
  2. dry with materialdried over with magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford the crude material
  5. customThe crude material was purified by flash column chromatography (eluant gradient elution 1-5% (9:1=methanol:ammonium hydroxide)/ethyl acetate)

Sources & evidence

ORD record
ord-fc2d4b98072c44c1aefce45d4caadd17
Source dataset
uspto-grants-2014_08
Patent number
US08809538B2

Reaction notes

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