Methanol → 1-Hydroxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide

HRID 251890Notes

Reaction equation

HRID 251890 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[N:17]=[CH:16][N:15]=[C:14]([NH:18][S:19](=[O:33])(=[O:32])[NH:20][CH:21]([O:24]CC3C=CC=CC=3)[CH2:22][CH3:23])[C:13]=2[C:34]2[CH:39]=[CH:38][C:37]([Br:40])=[CH:36][CH:35]=2)=[N:6][CH:7]=1.B(Br)(Br)Br.CO>C(Cl)Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Br:1][C:2]1[CH:7]=[N:6][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[N:17]=[CH:16][N:15]=[C:14]([NH:18][S:19](=[O:32])(=[O:33])[NH:20][CH:21]([OH:24])[CH2:22][CH3:23])[C:13]=2[C:34]2[CH:35]=[CH:36][C:37]([Br:40])=[CH:38][CH:39]=2)=[N:4][CH:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 1317286131-Benzyloxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide

Product 1

HCID 1317286141-Hydroxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amideYield 90.5%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-benzyloxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide (283 mg, 0.408 mmol) in DCM (15 mL) is cooled to −78° C. an then slowly treated with BBr3 (0.816 mL of a 1 M solution in DCM). The reaction mixture is allowed to warm to rt and stirring is continued for 1 h. Methanol (approx. 10 mL) is added to the suspension and stirring is continued for another 10 min before the mixture is diluted with 10% aq. citric acid solution (75 mL) and extracted with DCM (2×75 mL). The organic extracts are washed with water (50 mL), dried over MgSO4, filtered and concentrated. The crude product is purified on prep. tlc plates (silica gel, DCM with 10% methanol) to afford 1-hydroxypropanesulfamic acid[6-(2-(5-bromopyrimid-2-yloxy)-ethoxy)-5-(4-bromophenyl)-pyrimidin-4-yl]-amide (223 mg) as a pale grey foam. LC-MS: tR=0.92 min, [M+H]+=602.87; 1H NMR (CDCl3): δ 8.48 (s, 2H), 8.44 (s, 1H), 7.58-7.54 (m, 2H), 7.18-7.13 (m, 2H), 6.91 (s, 1H), 5.93 (t, J=6.4 Hz, 2H), 4.75-4.70 (m, 2H), 4.65-4.60 (m, 2H), 3.75 (t, J=5.2 Hz, 2H), 3.17 (q, J=6.4 Hz, 2H), 1.85-1.76 (m, 3H).

Workup

  1. stirringstirring
  2. waitis continued for another 10 min before the mixture
  3. extractionextracted with DCM (2×75 mL)
  4. washThe organic extracts are washed with water (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-8c43f542448f444d97cb9173046cf6fc
Source dataset
uspto-grants-2011_01
Patent number
US07868012B2

Reaction notes

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