Pyridine → Ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-chlorobenzyl)phosphonate

HRID 2279876Notes

Reaction equation

HRID 2279876 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:38]=[CH:37][C:27]([CH2:28][P:29](=[O:36])([O:33]CC)[O:30][CH2:31][CH3:32])=[CH:26][C:25]=3[Cl:39])[N:14]=2)=[CH:4][CH:3]=1.[I-].[Na+].N1C=CC=CC=1>>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:21])([F:20])[F:22])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:38]=[CH:37][C:27]([CH2:28][P:29](=[O:33])([OH:36])[O:30][CH2:31][CH3:32])=[CH:26][C:25]=3[Cl:39])[N:14]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 5238Sodium IodideHCID 86697815Diethyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-chlorobenzyl)phosphonate2×

Product 1

HCID 86697814Ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-chlorobenzyl)phosphonate

Procedure

A mixture of diethyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-chlorobenzyl)phosphonate (Compound 58C, 4.30 g, 6.60 mmol) and Sodium iodide (1.483 g, 9.896 mmol) in Pyridine (21.4 mL, 265 mmol) was heated to reflux for 18 hours. The pyridine was removed in vacuo and the remaining solids were taken up in water (˜50 mL). This was treated with 6N HCl, dropwise with stirring, until pH-2 was reached. A thick ppt formed. This mixture was extracted with DCM twice. The combined organic layers were dried over Na2SO4, filtered and concentrated to 3.719 g of a tan solid (90%). The material was used without further purification. 1H NMR (400 MHz, CDCl3) δ 12.57 (br. s., 1H) 8.81 (d, J=8.8 Hz, 1H) 8.33 (s, 1H) 8.08 (q, J=4.5 Hz, 1H) 7.83 (br. s., 1H) 7.35-7.44 (m, 2H) 7.19 (dt, J=8.3, 2.4 Hz, 1H) 4.06 (quin, J=7.3 Hz, 2H) 3.10 (d, J=22.0 Hz, 2H) 3.02 (d, J=5.1 Hz, 3H) 1.29 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 18 hours
  3. customThe pyridine was removed in vacuo
  4. additionThis was treated with 6N HCl
  5. customA thick ppt formed
  6. extractionThis mixture was extracted with DCM twice
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to 3.719 g of a tan solid (90%)
  10. customThe material was used without further purification

Sources & evidence

ORD record
ord-97f5d179292a4217a438ee92c087e030
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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