Dichloromethane → HCID 58386261, compound

HRID 64034Notes

Reaction equation

HRID 64034 reaction equation
C(Cl)Cl.[F:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([NH2:26])=[C:19]2[N:18]=1.CCN(C(C)C)C(C)C.Cl[C:37](=[O:42])[C:38]([O:40][CH3:41])=[O:39]>>[F:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([NH:26][C:37](=[O:42])[C:38]([O:40][CH3:41])=[O:39])=[C:19]2[N:18]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Product 1

HCID 58386261HCID 58386261, compoundYield 85%

Procedure

A DCM (5 mL, 0.7928 mmol) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 250 mg, 0.7928 mmol) and DIEA (0.2071 mL, 1.189 mmol) was first cooled in an ice-water bath, then methyl 2-chloro-2-oxoacetate (0.07657 mL, 0.8325 mmol) was added to reaction drop-wise. Ice bath was removed and the reaction was stirred at ambient temperature for approx. 10 minutes to reach completion. The reaction was washed with 10% citric acid (aqueous). The aqueous layer was back-washed with DCM. The combined organic layer was washed with 1:1 water/brine, dried (Na2SO4) and concentrated. The crude oil residue was directly purified by silica chromatography, eluting with EtOAc/hexanes 1:1 to 2:1, yielding the final product as a pale-yellowish foamy powder (270 mg, 85% yield). MS (apci) m/z=402.2 (M+H).

Workup

  1. customIce bath was removed
  2. washThe reaction was washed with 10% citric acid (aqueous)
  3. washThe aqueous layer was back-washed with DCM
  4. washThe combined organic layer was washed with 1:1 water/brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude oil residue was directly purified by silica chromatography
  8. washeluting with EtOAc/hexanes 1:1 to 2:1

Sources & evidence

ORD record
ord-73756f225d8449cca56c4a73fe72be1d
Source dataset
uspto-grants-2016_09
Patent number
US09447104B2

Reaction notes

Loading…