3-Aminopyridine → HCID 76283237, compound

HRID 1485298Notes

Reaction equation

HRID 1485298 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:26][CH2:25][CH2:24][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH:17]4[C:21]([OH:23])=O)[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1.[NH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=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>CN(C=O)C.O>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:26][CH2:25][CH2:24][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH:17]4[C:21]([NH:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[O:23])[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 100093-AminopyridineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86723634HCID 86723634, compound

Product 1

HCID 76283237HCID 76283237, compoundYield 10.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid (200 mg, 0.566 mmol) in DMF (2 mL) was added 3-amino pyridine (265 mg, 2.824 mmol), HATU (257 mg, 0.672 mmol) and DIPEA (0.166 mL, 0.902 mmol). The reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (2×25 mL). The organic layer was washed with water (8×30 mL) and dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave a crude product that was purified by reverse phase HPLC to afford 1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide (25 mg) as racemate. The enantiomers were separated by chiral HPLC to afford (R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide (10 mg). 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.56-0.70 (m, 2H), 0.78-0.87 (m, 2H), 1.69-1.81 (m, 1H), 2.00-2.19 (m, 4H), 2.21-2.39 (m, 2H), 2.68-2.81 (m, 4H), 3.58-3.72 (m, 1H), 3.78-3.89 (m, 1H), 4.65-4.78 (m, 1H), 6.25 (s, 1H), 7.33 (dd, 1H), 7.94 (s, 1H), 8.22 (d, 1H), 8.60 (s, 1H).

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. washThe organic layer was washed with water (8×30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customRemoval of EtOAc under reduced pressure
  5. customgave a crude product that
  6. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-76c0b0c7ab7d4fb1a04403bb2268ea8d
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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