Diisopropylethylamine → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide

HRID 2382118Notes

Reaction equation

HRID 2382118 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([C:17]2[N:22]=[CH:21][C:20]([C:23]([OH:25])=O)=[CH:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:50][C:51]1[CH:52]=[CH:53][C:54]2[O:59][CH2:58][CH2:57][N:56]([NH2:60])[C:55]=2[CH:61]=1>CN(C=O)C>[F:50][C:51]1[CH:52]=[CH:53][C:54]2[O:59][CH2:58][CH2:57][N:56]([NH:60][C:23]([C:20]3[CH:21]=[N:22][C:17]([C:13]4[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=4)=[N:18][CH:19]=3)=[O:25])[C:55]=2[CH:61]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450733632-(3-Fluorophenyl)pyrimidine-5-carboxylic acidHCID 68554248HCID 68554248, compound

Product 1

HCID 592000702-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amideYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (174 μL) is added to a mixture of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (218 mg), HATU (380 mg) and 6-fluoro-2,3-dihydro-benzo[1,4]oxazin-4-ylamine (220 mg) in DMF (15 mL) and then heated at 800 C. overnight. The reaction mixture is concentrated in vacuo and the residue is purified by silica gel column chromatography eluting with 30% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide (81 mg). MS: 369 (M+H); 1H NMR (300 MHz, DMSO-D6): δ 11.05 (s, 1H), 9.35 (s, 2H), 8.32 (dd, 1H), 8.18 (dd, 1H), 7.65 (m, 1H), 7.5 (m, 1H), 6.8-6.7 (m, 2H), 6.52-6.45 (m, 1H), 4.36-4.33 (m, 2H), 3.65 (m, 2H). IC50=12 nM.

Workup

  1. temperatureheated at 800 C
  2. customovernight
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. customthe residue is purified by silica gel column chromatography
  5. washeluting with 30% EtOAc in heptane

Sources & evidence

ORD record
ord-a5062436ed2542a395e9e7c9a7faa10b
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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