Ammonia → (S)-1,4,4-Trimethyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 1402285Notes

Reaction equation

HRID 1402285 reaction equation
[CH3:1][N:2]1[CH2:6][C:5]([CH3:8])([CH3:7])[CH2:4][C@H:3]1[C:9]([OH:11])=O.[F:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][NH2:20])=[N:17][CH:18]=1.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.N>C(Cl)Cl.CO>[F:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][NH:20][C:9]([C@@H:3]2[CH2:4][C:5]([CH3:7])([CH3:8])[CH2:6][N:2]2[CH3:1])=[O:11])=[N:17][CH:18]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 199167865-Fluoro-2-hydrazinylpyridineHCID 86687126L-Proline, 1,4,4-trimethyl-

Product 1

HCID 86687127(S)-1,4,4-Trimethyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 71.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Intermediate 87a (1.70 g, 5.00 mmol), (5-fluoro-pyridin-2-yl)-hydrazine (600 mg, 5.00 mmol) and DIPEA (1.29 g, 10.0 mmol) in DCM was added HATU (2.28 g, 6.00 mmol) and the mixture stirred at RT for 1 h. The reaction mixture was applied to an SCX-2 cartridge (70 g) and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as a yellow oil (950 mg, 71%). 1H NMR (400 MHz, CDCl3): 1.13 (3H, s), 1.15 (3H, s), 1.74 (1H, dd, J 12.5, 6.2), 2.12 (1H, dd, J 11.6, 10.0), 2.29 (1H, d, J 8.9), 2.46 (3H, s), 2.88 (1H, d, J 8.9), 3.15 (1H, dd, J 9.7, 6.5), 6.56-6.65 (2H, m), 7.28 (1H dt, J 8.6, 2.9), 8.03 (1H, d, J 2.5), 9.09 (1H, br s).

Workup

  1. washwashed with MeOH
  2. washThe product was eluted with 2M NH3 in MeOH
  3. concentrationconcentration in vacuo
  4. customgave a residue

Sources & evidence

ORD record
ord-4799cab01806412ca9c8a3897f241154
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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