Sodium Iodide → HCID 24954477, compound

HRID 386594Notes

Reaction equation

HRID 386594 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:14])[N:5]=[C:4]([CH:15]2[CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16]2)[CH:3]=1.[CH3:26][C:27]1[NH:31][N:30]=[C:29]([NH2:32])[CH:28]=1.CCN(C(C)C)C(C)C.[I-].[Na+]>CN(C=O)C>[NH:17]1[CH2:16][CH:15]([C:4]2[N:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[Cl:14])[N:7]=[C:2]([NH:32][C:29]3[CH:28]=[C:27]([CH3:26])[NH:31][N:30]=3)[CH:3]=2)[CH2:18]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 86638336HCID 86638336, compound

Product 1

HCID 24954477HCID 24954477, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 3-(6-chloro-2-(2-chlorophenyl)pyrimidin-4-yl)azetidine-1-carboxylate (280 mg, 0.74 mmol), 5-methyl-1H-pyrazol-3-amine (86 mg, 0.88 mmol), DIPEA (124 mg, 0.96 mmol) and sodium iodide (122 mg, 0.81 mmol) in DMF (5 mL) was heated at 120° C. overnight. The reaction mixture was concentrated and the residue partitioned between EtOAc and brine. After a further extraction with EtOAc, the combined organics were dried (MgSO4), filtered and concentrated. Purification was achieved by column chromatography (eluting with petroleum ether/ethyl acetate, 1/1). The residue was dissolved in TFA (1 mL) and DCM (3 mL) and stirred for 45 min and then concentrated. Purification by Gilson preparatory HPLC gave the azetidine as a white solid (32 mg, 13%). MS (ES+) m/e=341. 1H NMR: (DMSO) 2.23 (3H, s), 4.05-4.28 (5H, m), 6.25 (1H, s), 7.11 (1H, s), 7.43-7.65 (3H, m), 7.78 (1H, d), 8.97 (1H, s), 9.61 (1H, s), 10.47 (1H, s).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue partitioned between EtOAc and brine
  3. extractionAfter a further extraction with EtOAc
  4. dry with materialthe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification
  8. washwas achieved by column chromatography (eluting with petroleum ether/ethyl acetate, 1/1)
  9. dissolutionThe residue was dissolved in TFA (1 mL)
  10. concentrationconcentrated
  11. customPurification by Gilson preparatory HPLC

Sources & evidence

ORD record
ord-648987cde8c14003bd1c8fd328293725
Source dataset
uspto-grants-2013_02
Patent number
US08372850B2

Reaction notes

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