Diisopropylethylamine → 5-Chloro-4-(oxetan-3-yloxy)-pyridine-2-carboxylic acid ((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-amide

HRID 1480069Notes

Reaction equation

HRID 1480069 reaction equation
[Cl:1][C:2]1[C:3]([O:11][CH:12]2[CH2:15][O:14][CH2:13]2)=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:49][C@@H:50]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:51]([NH:53][CH3:54])=[O:52]>CN(C=O)C>[CH3:56][C:55]([CH3:58])([CH3:57])[C@H:50]([NH:49][C:8]([C:5]1[CH:4]=[C:3]([O:11][CH:12]2[CH2:15][O:14][CH2:13]2)[C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10])[C:51](=[O:52])[NH:53][CH3:54]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902034755-Chloro-4-(oxetan-3-yloxy)-pyridine-2-carboxylic acid

Product 1

HCID 762822505-Chloro-4-(oxetan-3-yloxy)-pyridine-2-carboxylic acid ((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-Chloro-4-(oxetan-3-yloxy)-pyridine-2-carboxylic acid (Example 23a, 35 mg, 152 μmol) in DMF (1 mL) was added HATU (58 mg, 152 μmol) and DIEA (66.6 μL, 381 μmol). The reaction mixture was then stirred at room temperature for 30 min, followed by addition of (S)-2-amino-N,3,3-trimethylbutanamide (CAN 89226-12-0, 22 mg, 152 μmol). The reaction mixture was stirred for 3 h. The crude reaction mixture was directly purified by preparative HPLC to deliver the desired compound (17.5 mg, 32%) as a yellow oil. MS (ESI, m/z): 356.5 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred for 3 h
  2. customThe crude reaction mixture
  3. customwas directly purified by preparative HPLC

Sources & evidence

ORD record
ord-f3611ac98d344a7fbe18200a54f2dd07
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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