Nitrogen → 1,1-Dimethylethyl (1S,4S)-5-[4-(5-fluoro-2-pyrimidinyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

HRID 1038027Notes

Reaction equation

HRID 1038027 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[CH2:10][N:11]2[C:15]1[CH:20]=[CH:19][C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:31]1[N:36]=[CH:35][C:34]([F:37])=[CH:33][N:32]=1.C([O-])([O-])=O.[K+].[K+].N#N>O.C(OCC)(=O)C.CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[CH2:10][N:11]2[C:15]1[CH:16]=[CH:17][C:18]([C:31]2[N:36]=[CH:35][C:34]([F:37])=[CH:33][N:32]=2)=[CH:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 5834662-Chloro-5-fluoropyrimidineHCID 66939367HCID 66939367, compound

Product 1

HCID 669399901,1-Dimethylethyl (1S,4S)-5-[4-(5-fluoro-2-pyrimidinyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylateYield 56.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

A mixed DMF/H2O (5 mL/5 mL) solution of (S,S)-5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (800 mg, 2 mmol), 2-chloro-5-fluoro-pyrimidine (340 mg, 2.6 mmol), K2CO3 (552 mg, 4 mmol) and Cl2Pd(dppf)CH2Cl2 (160 mg) was evacuated and recharged with N2 several times. The reaction was heated at 70° C. over 18 hrs. After cooling down to rt, 40 mL ethyl acetate and 10 mL water was added. The mixture was filtered through a pad of Celite and washed with additional ethyl acetate. The separated organic layer was dried (MgSO4) and concentrated. The crude was purified on silica gel column eluting with 50% ethyl acetate/hexanes to yield the title compound (420 mg) as a light yellow solid.

Workup

  1. temperatureAfter cooling down to rt
  2. filtrationThe mixture was filtered through a pad of Celite
  3. washwashed with additional ethyl acetate
  4. dry with materialThe separated organic layer was dried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude was purified on silica gel column
  7. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-7ad9d5f323f8403998121968b9697251
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

Loading…