Methanesulfonamide → HCID 78140968, compound

HRID 517901Notes

Reaction equation

HRID 517901 reaction equation
N=C=N.[OH:4][CH:5]1[C:14]2[C:9](=[N:10][C:11]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)[N:13]=2)[N:8]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([OH:37])=O)[CH2:7][CH2:6]1.C1CCC(NCC(F)=C2CCCCC2)CC1.[CH3:54][S:55]([NH2:58])(=[O:57])=[O:56]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[OH:4][CH:5]1[C:14]2=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)=[C:11]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)[N:10]=[C:9]2[N:8]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([NH:58][S:55]([CH3:54])(=[O:57])=[O:56])=[O:37])[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 72879MethanesulfonamideHCID 160435CarbodiimideHCID 23646088HCID 23646088, compoundHCID 66666112HCID 66666112, compound

Product 1

HCID 78140968HCID 78140968, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of polymer supported carbodiimide (1.36 mmol/g, 60 mg, 0.082 mmol) in DCM (dry) at RT (2 ml) under nitrogen was treated with (R or S)-7-(8-Hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid ([prepared according to the preparation procedures disclosed in PCT patent application PCT/EP2011/062028 Example 9.8a)(25 mg, 0.054 mmol), methanesulfonamide (5.17 mg, 0.054 mmol) followed by DMAP (6.65 mg, 0.054 mmol). The resulting orange suspension was stirred at RT overnight under an atmosphere of nitrogen. The reaction mixture was diluted with DCM (20 ml) and washed with 10% aqueous citric acid solution (20 ml×2), passing the organic portion through a phase separating column. The organic filtrate was concentrated under reduced pressure. Purification of the crude material by chromatography on silica eluting with EtOAc/iso-hexane followed by further purification by SFC (Chiralpak AD 250×10 mm; 30% IPA) afforded the titled compound;

Workup

  1. additionA suspension of polymer
  2. customat RT
  3. customprepared
  4. customaccording to the preparation procedures
  5. washwashed with 10% aqueous citric acid solution (20 ml×2)
  6. customseparating column
  7. concentrationThe organic filtrate was concentrated under reduced pressure
  8. customPurification of the crude material by chromatography on silica eluting with EtOAc/iso-hexane
  9. customfollowed by further purification by SFC (Chiralpak AD 250×10 mm; 30% IPA)

Sources & evidence

ORD record
ord-7d73e34f6b74466a916e2ad22c5a5e1e
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

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