Sodium hydride → 1-Benzyloxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide

HRID 251889Notes

Reaction equation

HRID 251889 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12](=[O:26])(=[O:25])[NH:13][CH:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][CH3:16])[C:6]=1[C:27]1[CH:32]=[CH:31][C:30]([Br:33])=[CH:29][CH:28]=1.[H-].[Na+].Cl[C:37]1[N:42]=[CH:41][C:40]([Br:43])=[CH:39][N:38]=1>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Br:43][C:40]1[CH:39]=[N:38][C:37]([O:1][CH2:2][CH2:3][O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12](=[O:26])(=[O:25])[NH:13][CH:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15][CH3:16])[C:6]=2[C:27]2[CH:28]=[CH:29][C:30]([Br:33])=[CH:31][CH:32]=2)=[N:42][CH:41]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 1317286121-Benzyloxypropanesulfamic acid[6-(2-hydroxyethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide

Product 1

HCID 1317286131-Benzyloxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amideYield 92.4%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-benzyloxypropanesulfamic acid[6-(2-hydroxyethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide (237 mg, 0.441 mmol) in THF (10 mL) is added NaH (58 mg, 60% dispersion in mineral oil, 1.32 mmol). The mixture is stirred for 5 min before 2-chloro-5-bromopyrimidine (128 mg, 0.662 mmol) is added. The reaction mixture is stirred at 60° C. for 2 h, diluted with 10% aq. citric acid solution (75 mL) and extracted with EA (75 mL). The organic extract is washed twice with water (2×50 mL) and concentrated. The remaining residue is purified on prep. tlc plates (silica gel, heptane/EA 1:1) to afford 1-benzyloxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide (283 mg) as a colourless foam. LC-MS: tR=1.09 min, [M+H]+=693.12; 1H NMR (CDCl3): δ 8.48 (s, 2H), 8.34 (s, 1H), 7.58-7.53 (m, 2H), 7.38-7.28 (m, 5H), 7.16-7.11 (m, 2H), 6.84 (s, 1H), 5.97 (t, J=5.9 Hz, 1H), 4.73-4.68 (m, 2H), 4.64-4.60 (m, 2H), 4.50 (s, 2H), 3.56 (t, J=5.9 Hz, 2H), 3.17 (q, J=6.4 Hz, 2H), 1.88 (p, J=5.9 Hz, 2H).

Workup

  1. additionis added
  2. extractionextracted with EA (75 mL)
  3. extractionThe organic extract
  4. washis washed twice with water (2×50 mL)
  5. concentrationconcentrated
  6. customThe remaining residue is purified on prep

Sources & evidence

ORD record
ord-4259f46dab1340c5b24e464a122cef67
Source dataset
uspto-grants-2011_01
Patent number
US07868012B2

Reaction notes

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