Potassium Carbonate → [2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl ester

HRID 2220141

Reaction equation

HRID 2220141 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:23])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)=[CH:4][C:3]=1[NH:24][C:25]1[N:30]=[C:29]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[CH:28]=[CH:27][N:26]=1.Br[CH2:38][CH2:39][P:40](=[O:47])([O:44][CH2:45][CH3:46])[O:41][CH2:42][CH3:43].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:42]([O:41][P:40]([CH2:39][CH2:38][N:20]1[CH2:19][CH2:18][N:17]([CH2:16][C:13]2[CH:12]=[CH:11][C:10]([C:9](=[O:23])[NH:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:24][C:25]4[N:30]=[C:29]([C:31]5[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=5)[CH:28]=[CH:27][N:26]=4)[CH:4]=3)=[CH:15][CH:14]=2)[CH2:22][CH2:21]1)(=[O:47])[O:44][CH2:45][CH3:46])[CH3:43]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79218Diethyl (2-bromoethyl)phosphonateHCID 9869737Cgp-74588

Product 1

HCID 59772964[2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl esterYield 72.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-piperazin-1-ylmethyl-benzamide (30 mg, 0.06 mmol, Zimmermann et al., Bioorg. Med. Chem. Lett. 1996, 6, 1221), diethyl 2-bromoethylphosphonate (30 μL, 0.12 mmol) and K2CO3 (20 mg, 0.16 mmol) in 2.5 mL of DMF was heated at 110° C. for 8 hours when most of the starting materials were consumed as judged by LCMS analysis. The solid material was filtered off. The filtrate was diluted with water and then extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to dryness. The crude material was purified by silica gel chromatography using 10% MeOH/CH2Cl2 to provide 28 mg (55%) of the desired product. 1H NMR (300 MHz, CDCl3) δ 1.32 (t, 6H), 1.92-20.3 (m, 4H), 2.35 (s, 3H), 2.5 (bs, 6H), 2.64 (m, 2H), 3.56 (s, 2H), 4.05-4.14 (m, 4H), 7.07(s, 1H), 7.18 (d, 2H, J=5 Hz), 7.30 (dd, 1H, J=6, 8 Hz), 7.33-7.45 (m, 3H), 7.84 (d, 2H, J=8 Hz), 8.01 (s, 1H), 8.51 (dd, 2H, J=4, 9 Hz), 8.58 (d, 1H, J=2 Hz), 8.70 (dd, 1H, J=2, 5 Hz), 9.25 (s, 1H); 31P (121.4 MHz, CDCl3) δ 30.5; MS (m/z) 644 [M+H]+.

Workup

  1. customwere consumed
  2. filtrationThe solid material was filtered off
  3. additionThe filtrate was diluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5196580ba9e34eedbf953266b82dbf80
Source dataset
uspto-grants-2008_08
Patent number
US07417055B2

Linked notes

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