Triethylamine → N-((1R,3S)-3-((2-Chloro-5-fluoropyrimidin-4-yl)amino)cyclohexyl)pyrrolidine-1-carboxamide

HRID 539913Notes

Reaction equation

HRID 539913 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11](C(O)=O)[CH2:10]2)[C:5]([F:18])=[CH:4][N:3]=1.N(P([O:31][C:32]1C=CC=CC=1)(OC1C=CC=CC=1)=O)=[N+]=[N-].C([N:40](CC)CC)C.[NH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1>C1COCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([NH:40][C:32]([N:45]3[CH2:49][CH2:48][CH2:47][CH2:46]3)=[O:31])[CH2:10]2)[C:5]([F:18])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 123414Diphenylphosphoryl azideHCID 86667448(1R,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanecarboxylic acid

Product 1

HCID 86667450N-((1R,3S)-3-((2-Chloro-5-fluoropyrimidin-4-yl)amino)cyclohexyl)pyrrolidine-1-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

A solution of (1R,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexane-carboxylic acid, 20, (8.2 g, 30.0 mmol), (azido(phenoxy)phosphoryl)oxybenzene (9.7 mL, 45.0 mmol) and triethylamine (5.8 mL, 42.0 mmol) in THF (200 mL) was degassed under nitrogen for 15 minutes. The reaction mixture was heated at 85° C. for 30 minutes. To the reaction mixture was added pyrrolidine (7.5 mL, 90.0 mmol) and the reaction was heated at 85° C. for an additional 15 min. The mixture was diluted into brine and extracted with EtOAc. The organic phase was separated, dried over MgSO4. The product was isolated (6.25 g) by filtration after partial removal of solvent in vacuo: 1H NMR (300 MHz, CDCl3) δ 7.87 (d, J=2.8 Hz, 2H), 5.04 (d, J=8.1 Hz, 2H), 4.09 (ddd, J=26.9, 13.4, 5.6 Hz, 4H), 3.91-3.71 (m, 2H), 3.32 (t, J=6.5 Hz, 7H), 2.45 (d, J=11.5 Hz, 2H), 2.08 (dd, J=22.1, 12.0 Hz, 4H), 1.96-1.82 (m, 9H), 1.54 (dd, J=18.6, 8.5 Hz, 2H), 1.22-1.01 (m, 6H).

Workup

  1. temperaturethe reaction was heated at 85° C. for an additional 15 min
  2. extractionextracted with EtOAc
  3. customThe organic phase was separated
  4. dry with materialdried over MgSO4
  5. customThe product was isolated (6.25 g)
  6. filtrationby filtration
  7. customafter partial removal of solvent in vacuo

Sources & evidence

ORD record
ord-8f018946072f4ac4ac5567ebc0e405bc
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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