1-[(2,2-Difluorocyclopropyl)methyl]-5-(1,2,3,3a,4,6a-hexahydrocyclo-penta-[c]pyrrol-5-yl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide → 1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-(octahydrocyclopenta[c]-pyrrol-5-yl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

HRID 629896Notes

Reaction equation

HRID 629896 reaction equation
[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH2:16][CH:17]4[CH2:21][NH:20][CH2:19][CH:18]4[CH:22]=3)=[CH:12][CH:13]=2)[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]>[Pd].CO>[F:26][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([CH:15]3[CH2:16][CH:17]4[CH2:21][NH:20][CH2:19][CH:18]4[CH2:22]3)=[CH:12][CH:13]=2)[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]

Participants

4

Reactant 1

HCID 711367261-[(2,2-Difluorocyclopropyl)methyl]-5-(1,2,3,3a,4,6a-hexahydrocyclo-penta-[c]pyrrol-5-yl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

Product 1

HCID 711407481-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-(octahydrocyclopenta[c]-pyrrol-5-yl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

1-[(2,2-Difluorocyclopropyl)methyl]-5-(1,2,3,3a,4,6a-hexahydrocyclo-penta-[c]pyrrol-5-yl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (24-2, 100 mg, 0.26 mmol, 1.0 equiv) was added to anhydrous methanol (2.6 mL). To this solution was added 10% palladium(0) on carbon (55.7 mg, 0.052 mmol, 0.2 equiv) to give a black suspension. The reaction flask was evacuated and back-filled with hydrogen from a balloon. This process was repeated an additional 2 times. The resulting mixture was allowed to stir under an atmosphere of H2 for 30 min. Following this duration, LCMS showed complete consumption of starting material. The reaction contents were filtered through Celite, washed with DCM and concentrated to give 25-1 as an off-white solid. The crude material was carried forward without additional purification.

Workup

  1. customto give a black suspension
  2. customThe reaction flask was evacuated
  3. additionback-filled with hydrogen from a balloon
  4. customconsumption of starting material
  5. customThe reaction contents
  6. filtrationwere filtered through Celite
  7. washwashed with DCM
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3a3c5a8a7eaf40ca964c197cb8e16bf1
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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