Picolinic acid → HCID 71536959, compound

HRID 1503270Notes

Reaction equation

HRID 1503270 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]12[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][C:11]([NH2:19])([CH2:12]3)[CH2:10]1)[CH2:16]2.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26](O)=[O:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]12[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][C:11]([NH:19][C:26]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=4)=[O:27])([CH2:12]3)[CH2:10]1)[CH2:16]2

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117702497HCID 117702497, compound

Product 1

HCID 71536959HCID 71536959, compoundYield 116.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of intermediate 11, 3-(pyrazin-2-ylethynyl)-1-adamantylamine (30 mg, 0.12 mmol) and picolinic acid (18 mg, 0.15 mmol) in DMF (2 mL) was added DIEA (50 mg, 0.38 mmol) and HATU (60 mg, 0.12 mmol) under N2. After stirring at room temperature for an hour, the reaction was quenched with brine and extracted with ethyl acetate (2×20 mL). The combined organic phase was washed with brine, dried over Na2SO4, and concentrated under reduced pressure to give a residue, which was purified by Prep HPLC to give 50 mg (95%) of the title compound, pyridine-2-carboxylic acid (3-pyrazin-2-ylethynyl-adamantan-1-yl)-amide, as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 8.60-8.43 (m, 4H), 8.17 (d, J=8.0 Hz, 1H), 7.96 (s, 1H), 7.85-7.82 (m, 1H), 7.42-7.39 (m, 1H), 2.45 (s, 2H), 2.26-2.20 (m, 4H), 2.11-1.97 (m, 6H), 1.76-1.69 (m, 2H); ESI-MS m/z: 359 (M+H)+.

Workup

  1. customthe reaction was quenched with brine
  2. extractionextracted with ethyl acetate (2×20 mL)
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue, which
  7. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-d01cb91c14b44b94adc4f07c9b3720da
Source dataset
uspto-grants-2015_12
Patent number
US09212165B2

Reaction notes

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