Acetic Acid → N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide

HRID 1969875Notes

Reaction equation

HRID 1969875 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]=O)=[CH:6][N:5]=[C:4]2[N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:13]=[CH:14][C:3]=12.[CH2:25]([C@H:27]1[C@@H:31]([N:32]=C=O)[CH2:30][C@@H:29]([NH:35][S:36]([CH:39]2[CH2:41][CH2:40]2)(=[O:38])=[O:37])[CH2:28]1)[CH3:26].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(Cl)Cl>[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH2:10][NH:32][C@@H:31]2[C@H:27]([CH2:25][CH3:26])[CH2:28][C@H:29]([NH:35][S:36]([CH:39]3[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:30]2)=[CH:6][N:5]=[C:4]2[N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:13]=[CH:14][C:3]=12

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 585575753-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanalHCID 58557883N-((1S,3R,4S)-3-ethyl-4-isocyanatocyclopentyl)cyclopropanesulfonamide

Product 1

HCID 58557549N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamideYield 55%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal (0.420 g, 1.04 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide (0.290 g, 1.25 mmol, prepared using OOO from Example #23 step E with NaOH) in DCE (4.00 mL) was added glacial acetic acid (0.089 mL, 1.6 mmol). The reaction mixture stirred for about 15 min at ambient temperature and sodium triacetoxyborohydride (0.331 g, 1.56 mmol) was added. The reaction was left stirring at ambient temperature for about 72 h. Saturated aqueous NaHCO3 (about 5 mL) was slowly added followed by DCM (5 mL). The layers were separated and the aqueous phase was extracted with DCM (2×5 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The remaining yellow oil was purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in heptane to give N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclo-propanesulfonamide (0.330 g, 55%) as a white foam: LC/MS (Table 1, Method b) Rt=2.10 min; MS m/z: 579 (M+H)+.

Workup

  1. waitThe reaction was left
  2. stirringstirring at ambient temperature for about 72 h
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with DCM (2×5 mL)
  5. dry with materialThe combined organics were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe remaining yellow oil was purified by silica gel chromatography
  9. washeluting with a gradient of 0-50% EtOAc in heptane

Sources & evidence

ORD record
ord-76f963c714d94da4a8cda69f8d8167f4
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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