Dichloromethane → HCID 68007768, compound

HRID 527038Notes

Reaction equation

HRID 527038 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][OH:25])[CH2:19]4)[C:14]([F:26])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[O:37]=[C:38]=[N:39][C:40](Cl)=[O:41].C(Cl)Cl.C[O-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([N:24]5[C:40](=[O:41])[NH:39][C:38](=[O:37])[O:25]5)[CH2:19]4)[C:14]([F:26])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 119708Isocyanatocarbonyl chlorideHCID 10942334Sodium MethoxideHCID 86667438HCID 86667438, compound

Product 1

HCID 68007768HCID 68007768, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-((1S,3R)-3-(hydroxyamino)cyclohexyl)pyrimidin-4-amine, 55b, (0.072 g, 0.136 mmol) in THF (2 mL) at 0° C. was added N-(oxomethylene)carbamoyl chloride (0.014 mL, 0.176 mmol). A white solid formed immediately. The slurry was shaken and sonicated to make an even suspension/slurry. Then, —CH2Cl2 (1 mL)) was added to help solvate the slurry. After 135 min, the mixture was treated with NaOMe (2 mL, 25% w/v). After 2 min, the mixture was quenched with saturated NH4Cl and acidified with 1M HCl. The mixture was extracted with EtOAc (3×) and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Preparative HPLC provided the desired product (25 mg).

Workup

  1. customA white solid formed immediately
  2. customsonicated
  3. waitAfter 2 min
  4. customthe mixture was quenched with saturated NH4Cl
  5. extractionThe mixture was extracted with EtOAc (3×)
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-62783e8ff6f2499390afb8b2b950341f
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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