Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 4-(tert-butyldimethylsilyloxy)-2-ethyl-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide

HRID 1969916Notes

Reaction equation

HRID 1969916 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][C@H:12]([C:14]([OH:16])=O)[C@H:11]([CH2:17][CH3:18])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH:19]([C:21]1[N:22]=[C:23]2[CH:29]=[CH:28][N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[C:24]2=[N:25][CH:26]=1)[NH2:20].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.[Si](O[C@H]1C[C@H](C(NNC2N=C3C=CN(S(C4C=CC(C)=CC=4)(=O)=O)C3=NC=2)=O)[C@H](CC)C1)(C(C)(C)C)(C)C>[Si:1]([O:8][CH:9]1[CH2:13][CH:12]([C:14]([NH:20][NH:19][C:21]2[N:22]=[C:23]3[CH:29]=[CH:28][N:27]([S:30]([C:33]4[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=4)(=[O:32])=[O:31])[C:24]3=[N:25][CH:26]=2)=[O:16])[CH:11]([CH2:17][CH3:18])[CH2:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazineHCID 67998141(1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentanecarboxylic acid

Product 1

HCID 585573274-(tert-butyldimethylsilyloxy)-2-ethyl-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 67998395(1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-ethyl-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazideSolvent

Procedure

To a scalemic mixture enriched in (1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentanecarboxylic acid (1.62 g, 5.96 mmol) in DCM (60 mL) was added 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (Example #1, Step D, 1.86 g, 6.13 mmol), HATU (2.38 g, 6.26 mmol) and TEA (3.32 mL, 23.8 mmol). The reaction mixture was stirred at ambient temperature for about 1 h. The reaction mixture was diluted with DCM (200 mL), washed with water (50 mL) and brine (50 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The residue was purified using silica gel chromatography eluting with 0-30% EtOAc in DCM to give a scalemic mixture enriched in (1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-ethyl-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide (2.64 g, 79%) as a brown solid: LC/MS (Table 1, Method b) Rt=3.20 min; MS m/z: 558 (M+H)+.

Workup

  1. washwashed with water (50 mL) and brine (50 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. customThe residue was purified
  5. washeluting with 0-30% EtOAc in DCM
  6. customto give a scalemic mixture

Sources & evidence

ORD record
ord-ceb78aded3144a6cb2dd689b8417c840
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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