Cyclopropanecarboxaldehyde → 4-(6-bromo-2-cyclopropyl-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine

HRID 1398508Notes

Reaction equation

HRID 1398508 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=1.[CH:17]1([CH:20]=O)[CH2:19][CH2:18]1.OOS([O-])=O.[K+]>CN(C=O)C.CCOC(C)=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[C:20]([CH:17]3[CH2:19][CH2:18]3)[N:9]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:3]=2[CH:4]=1

Participants

6

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 23707502Potassium hydroxy sulfiteHCID 681818104-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine

Product 1

HCID 681817554-(6-bromo-2-cyclopropyl-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine (400 mg, 1.43 mmol) in DMF (4 mL) were added cyclopropanecarbaldehyde (130 mg, 1.86 mmol) and oxone (527 mg, 0.86 mmol). The reaction was stirred at RT for 3 days. The mixture was diluted with EtOAc (20 mL) and washed with water. The aqueous layer was extracted with more EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (Isolute column, 100% DCM to 2% MeOH/DCM) afforded the title compound as an orange solid: 1H NMR (500 MHz, MeOD) δ 1.16-1.24 (2H, m), 1.24-1.29 (2H, m), 2.32-2.48 (1H, m), 6.98 (1H, d, J=5.36 Hz), 7.41-7.45 (1H, m), 7.47-7.52 (1H, m), 7.90 (1H, d, J=1.89 Hz), 8.51 (1H, d, J=5.20 Hz); LC-MS (Method B): m/z=+330.0, 331.8 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with more EtOAc
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (Isolute column, 100% DCM to 2% MeOH/DCM)

Sources & evidence

ORD record
ord-88fa5fdb471a43f99cb0a4e019655ef5
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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