Diisopropylethylamine → N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

HRID 2237159Notes

Reaction equation

HRID 2237159 reaction equation
ClC1C=C(OC2C=CC=CC2(N)F)N=CN=1.[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31]C(NC(=O)CC3C=CC(F)=CC=3)=S)=[CH:27][C:26]=2[F:45])[CH:19]=1.[F:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:59])[CH2:55][C:56]([OH:58])=O)=[CH:49][CH:48]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:56](=[O:58])[CH2:55][C:54]([NH:53][C:50]3[CH:49]=[CH:48][C:47]([F:46])=[CH:52][CH:51]=3)=[O:59])=[CH:27][C:26]=2[F:45])[CH:19]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acid2×HCID 115538441-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thioureaHCID 866014734-Chloro-6-(2-amino-2-fluorophenoxy)pyrimidine

Product 1

HCID 59852939N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-chloro-6-(2-amino-2-fluorophenoxy)pyrimidine (29 mg, 0.12 mmol, Compound B of Example 2), 3-(4-fluorophenylamino)-3-oxopropanoic acid (26 mg, 0.13 mmol, Compound B of Example 1) in DMF (1.5 mL) was treated with DIPEA (24 μl, 0.14 mmol) and TBTU (46 mg, 0.14 mmol). The reaction mixture was stirred at RT overnight, diluted with EtOAc (25 mL), and the organic phase was washed with brine (3×20 mL), dried (MgSO4) and concentrated. The product was purified by flash chromatography using 1-3% MeOH in CH2Cl2 as the eluent to give the title compound as a white solid (35 mg, 78%). 1H NMR (DMSO-d6) δ 10.49 (s, 1H), 10.25 (s, 1H), 8.65 (s, 1H), 7.78 (d, 1H, J=12.1 Hz), 7.63-7.57 (m, 3H), 7.40-7.34 (m, 2H), 7.16 (t, 2H, J=8.8 Hz), 3.48 (s, 2H); MS(ESI+) m/z 419.21 (M+H)+.

Workup

  1. washthe organic phase was washed with brine (3×20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe product was purified by flash chromatography

Sources & evidence

ORD record
ord-d67e0df3acd846859469440f1a8191f3
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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