Formaldehyde → 2-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

HRID 2067875Notes

Reaction equation

HRID 2067875 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](N(OC)C)=[O:17])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C=[O:23].[O-:24][CH2:25]C.[Na+].[OH-].[K+]>CS(C)=O.O.CCO>[Br:1][C:2]1[CH:7]=[N:6][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH:15]([CH2:16][OH:17])[C:25]([OH:24])=[O:23])=[CH:13][CH:14]=2)=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 14797Potassium HydroxideHCID 2723922Sodium ethoxideHCID 866601182-(4-(5-bromopyrimidin-2-ylamino)phenyl)-N-methoxy-N-methylacetamide

Product 1

HCID 687270502-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

2-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-N-methoxy-N-methylacetamide 23 (2.0 mmol), paraformaldehyde (6.0 mmol) and sodium ethoxide (12.0 mmol) are dissolved in DMSO (10 mL). The reaction mixture is stirred at rt for 1 h. Then a solution of KOH (12.0 mmol) in H2O (5.0 mL) and EtOH (5.0 mL) is added. The reaction mixture is heated at 50° C. for 5 h. After the reaction is completed, the reaction mixture is washed with DCM (50 mL). The aqueous phase is acidified to pH ˜5 and extracted with DCM (2×50 mL). The organic layer is separated, dried and concentrated to yield 2-(4-(5-bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 25, which is used in the next step without further purification. 1H NMR (400 MHz, d6-DMSO) δ 12.30 (bs, 1H), 9.84 (s, 1H), 8.57 (s, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 3.90 (t, J=8.8 Hz, 1H), 3.49-3.61 (m, 2H), 3.35 (bs, 1H). MS (m/z) (M+1)+: 338.0, 340.0.

Workup

  1. temperatureThe reaction mixture is heated at 50° C. for 5 h
  2. washthe reaction mixture is washed with DCM (50 mL)
  3. extractionextracted with DCM (2×50 mL)
  4. customThe organic layer is separated
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4efbbeb8cdc24914bded4f766cf1741c
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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