Diisopropylethylamine → 5-Chloro-4-cyclobutylmethoxy-pyridine-2-carboxylic acid ((R)-1-hydroxymethyl-1,2-dimethyl-propyl)-amide

HRID 1480054Notes

Reaction equation

HRID 1480054 reaction equation
[Cl:1][C:2]1[C:3]([O:11][CH2:12][CH:13]2[CH2:16][CH2:15][CH2:14]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.[NH2:41][C@:42]([CH3:48])([CH:45]([CH3:47])[CH3:46])[CH2:43][OH:44].CCN(C(C)C)C(C)C>C(#N)C>[OH:44][CH2:43][C@@:42]([NH:41][C:8]([C:5]1[CH:4]=[C:3]([O:11][CH2:12][CH:13]2[CH2:16][CH2:15][CH2:14]2)[C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10])([CH3:48])[CH:45]([CH3:47])[CH3:46]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12113027R-2-Amino-2,3-dimethyl-butan-1-OLHCID 902036505-Chloro-4-cyclobutylmethoxy-pyridine-2-carboxylic acid

Product 1

HCID 762824845-Chloro-4-cyclobutylmethoxy-pyridine-2-carboxylic acid ((R)-1-hydroxymethyl-1,2-dimethyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-chloro-4-cyclobutylmethoxy-pyridine-2-carboxylic acid (60 mg, 249 μmol) in acetonitrile (2 mL) was added HATU (123 mg, 324 μmol), (2R)-2-amino-2,3-dimethyl-1-butanol (CAN 155158-75-1, 32.1 mg, 274 μmol) and DIEA (217 μL, 1.25 mmol). The brownish reaction mixture was stirred for 18 h at room temperature. The crude reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient) and finally chiral chromatography (ChiralPak AD, heptane/ethanol 9:1) to deliver the desired compound (27.3 mg, 43%) as colorless oil. MS (ESI, m/z): 341.1 (MH+).

Workup

  1. customThe brownish reaction mixture
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. customthe residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient) and finally chiral chromatography (ChiralPak AD, heptane/ethanol 9:1)

Sources & evidence

ORD record
ord-6f117c21c45b45b78d1a40ac35841894
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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