Diisopropylethylamine → HCID 23634343, compound

HRID 2039672Notes

Reaction equation

HRID 2039672 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:3]=1.Cl[C:13](Cl)([O:15]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.[CH3:33][NH:34][C:35]([C:37]1[CH:42]=[C:41]([O:43][C:44]2[CH:49]=[CH:48][C:47]([NH2:50])=[C:46]([F:51])[CH:45]=2)[CH:40]=[CH:39][N:38]=1)=[O:36]>C1COCC1.CN(C=O)C>[CH3:33][NH:34][C:35]([C:37]1[CH:42]=[C:41]([O:43][C:44]2[CH:49]=[CH:48][C:47]([NH:50][C:13]([NH:1][C:2]3[CH:3]=[C:4]([C:8]([CH3:11])([CH3:10])[CH3:9])[N:5]=[CH:6][N:7]=3)=[O:15])=[C:46]([F:51])[CH:45]=2)[CH:40]=[CH:39][N:38]=1)=[O:36]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 7137446-tert-butylpyrimidin-4-amineHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Product 1

HCID 23634343HCID 23634343, compoundYield 63.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 6-amino-4-t-butylpyrimidine (20.0 mg; 0.13 mmol), triphosgene (14.52 mg; 0.05 mmol) and diisopropylethylamine (20.51 mg; 0.16 mmol) in THF (0.7 mL) was heated at 70° C. for 4 h. A solution of 4-(4-amino-3-fluoro-phenoxy)-pyridine-2-carboxylic acid methylamide (34.5 mg; 0.13 mmol) in DMF (1.5 mL) was then added and the reaction mixture was heated at 70° C. for another 8 h, then extracted between EtOAc and saturated aqueous NaHCO3. The organic layer was dried and evaporated under reduced pressure to give a crude oil that was purified via HPLC to give the title compound (14 mg, 9%). 1H-NMR (CD3OD) δ 8.73 (s, 1H), 8.48 (d, J=4.0 Hz, 1H), 8.29 (t, J=4.0 Hz, 1H), 7.57 (d, J=4.0 Hz, 1H), 7.58-7.08 (m, 3H), 7.01 (s, 1H), 2.94 (s, 3H), 1.36 (s, 9H). LC-MS m/z 439 [M+H]+.

Workup

  1. extractionextracted between EtOAc and saturated aqueous NaHCO3
  2. customThe organic layer was dried
  3. customevaporated under reduced pressure
  4. customto give a crude oil that
  5. customwas purified via HPLC

Sources & evidence

ORD record
ord-fc7ca586a3ff47dc839b366b97e387d5
Source dataset
uspto-grants-2013_11
Patent number
US08580798B2

Reaction notes

Loading…