Diisopropylethylamine → HCID 89691015, compound

HRID 877537Notes

Reaction equation

HRID 877537 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=2)[C:5]([C:18]2[S:19][C:20]([C:23]([N:25]3[CH2:29][CH2:28][C@@H:27]([OH:30])[CH2:26]3)=[O:24])=[N:21][N:22]=2)=[CH:4][N:3]=1.C[CH2:32][N:33](C(C)C)C(C)C.Cl.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([NH:33][CH3:32])=[O:14])=[CH:16][CH:17]=2)[C:5]([C:18]2[S:19][C:20]([C:23]([N:25]3[CH2:29][CH2:28][C@@H:27]([OH:30])[CH2:26]3)=[O:24])=[N:21][N:22]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89690976HCID 89690976, compound

Product 1

HCID 89691015HCID 89691015, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (R)-4-((2-chloro-5-(5-(3-hydroxypyrrolidine-1-carbonyl)-1,3,4-thiadiazol-2-yl)pyridin-4-yl)amino)benzoic acid (15) (150 mg, 0.336 mmol) in DMF (10 mL), DIPEA (1.682 mmol, 5 equiv.), methanamine HCl (3.36 mmol, 10 equiv.) and HATU (0.673 mmol, 2 equiv.) were added at room temperature. The reaction mixture was allowed to stir overnight at ambient temperature. The reaction mixture was evaporated to remove excess of DMF. The residue obtained was then diluted with water and extracted using EtOAc. The organic layer was dried over Na2SO4, filtered and evaporated to get crude compound. The crude compound was purified by column chromatography through silica gel and MeOH: DCM as eluent to isolate the desired compound, (R)-4-((2-chloro-5-(5-(3-hydroxypyrrolidine-1-carbonyl)-1,3,4-thiadiazol-2-yl)pyridin-4-yl)amino)-N-methylbenzamide (16). LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 0.71 min; LCMS (ES-API), m/z 459.63 (M+H).

Workup

  1. customThe reaction mixture was evaporated
  2. customto remove excess of DMF
  3. customThe residue obtained
  4. extractionextracted
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto get crude compound
  9. customThe crude compound was purified by column chromatography through silica gel and MeOH

Sources & evidence

ORD record
ord-1f930ead83624b91a25ee77a58bca827
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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