Diisopropylethylamine → 2-Chloro-6-morpholin-4-yl-pyrimidine-4-carboxylic acid[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amide

HRID 1641267Notes

Reaction equation

HRID 1641267 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[N:50]1([CH2:56][CH2:57][O:58][C:59]2[C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[C:62]([NH2:69])=[CH:61][CH:60]=2)[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>CN(C=O)C.O>[N:50]1([CH2:56][CH2:57][O:58][C:59]2[C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[C:62]([NH:69][C:8]([C:6]3[CH:5]=[C:4]([N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)[N:3]=[C:2]([Cl:1])[N:7]=3)=[O:10])=[CH:61][CH:60]=2)[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110439124-(2-Morpholinoethoxy)naphthalen-1-amineHCID 184220792-Chloro-6-morpholinopyrimidine-4-carboxylic acid

Product 1

HCID 595532362-Chloro-6-morpholin-4-yl-pyrimidine-4-carboxylic acid[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amideYield 83.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Chloro-6-morpholin-4-ylpyrimidine-4-carboxylic acid (0.280 g, 1.15 mmol) in DMF (5 ml) is treated with HBTU (0.466 g, 1.5 eq) and diisopropylethylamine (0.367 ml). The mixture is stirred at room temperature for 5-10 min. 4-(2-Morpholin-4-yl-ethoxy)-naphthalen-1-ylamine (0.224 g, 0.82 mmol) is then added. The mixture is stirred at room temperature for an additional 15 h, diluted with water and extracted with ethyl acetate. The organic layer is dried over Na2SO4 and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 2% MeOH in ethyl acetate to provide 2-chloro-6-morpholin-4-yl-pyrimidine-4-carboxylic acid[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amide as a solid (0.342 g). Mp: 95-93° C., 1H NMR (300 MHz, DMSOd6) δ 10.43 (s, 1H), 8.20 (m, 1H), 7.79 (s, 1H), 7.56 (m, 3H), 7.39 (s, 1H), 7.03 (d, J=8.1 Hz, 1H), 4.31 (t, J=6.3 Hz, 2H), 3.60 (brt, 8H) 2.88 (t, 2H), 2.56 (brt, 8H). MS: 498 (M+1).

Workup

  1. stirringThe mixture is stirred at room temperature for an additional 15 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer is dried over Na2SO4
  4. customevaporated to dryness
  5. customThe residue is purified by column chromatography on silica gel
  6. washeluted with 2% MeOH in ethyl acetate

Sources & evidence

ORD record
ord-155ddc844cab4df8b35f0f99257f18ca
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

Loading…