1,2-Dichloroethane → HCID 51353730, compound

HRID 2367275Notes

Reaction equation

HRID 2367275 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([C:15](O)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[C:20]([F:26])[CH:19]=2)[N:3]=1.[CH:27]1[CH:28]=[CH:29][C:30]2N(O)N=[N:33][C:31]=2[CH:32]=1.C(Cl)CCl.NC1C=CC=CC=1>CCOC(C)=O.CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([C:15]([NH:33][C:31]3[CH:32]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[C:20]([F:26])[CH:19]=2)[N:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 6115AnilineHCID 757711-HydroxybenzotriazoleHCID 51353728HCID 51353728, compound

Product 1

HCID 51353730HCID 51353730, compoundYield 67.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 5 mL vial was charged with (2S,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-2-morpholinecarboxylic acid (72 mg, 0.201 mmol), HOBT (29.9 mg, 0.222 mmol) and DMF (1 mL) under nitrogen. The mixture was stirred and cooled in an ice bath and then EDC (42.5 mg, 0.222 mmol) was added. After stirring 10 minutes, aniline (0.020 mL, 0.222 mmol) was added and the mixture was allowed to warm to room temperature and stir. At 2 and 4 hours, there was no change in progress. The mixture was diluted with EtOAc and washed with water, saturated NaHCO3, brine, and dried (MgSO4). After filtering, the filtrate was concentrated and the product was purified by silica gel chromatography (Analogix SF-4-g) eluting with 20-50% EtOAc—CHCl3 to afford the title compound (59 mg) as a light orange oil. LC-MS (ES) m/z=433 [M+H]+.

Workup

  1. temperaturecooled in an ice bath
  2. stirringAfter stirring 10 minutes
  3. stirringstir
  4. customAt 2 and 4 hours, there
  5. washwashed with water, saturated NaHCO3, brine
  6. dry with materialdried (MgSO4)
  7. filtrationAfter filtering
  8. concentrationthe filtrate was concentrated
  9. customthe product was purified by silica gel chromatography (Analogix SF-4-g)
  10. washeluting with 20-50% EtOAc—CHCl3

Sources & evidence

ORD record
ord-23a78362b5604d25bed13661627ed5f8
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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