Methanesulfonyl chloride → 1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-[2-(methylsulfonyl)-1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

HRID 629898Notes

Reaction equation

HRID 629898 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].CCN(C(C)C)C(C)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C(#N)C>[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]([C:15]3[CH2:16][CH:17]4[CH2:21][N:20]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:19][CH:18]4[CH:22]=3)=[CH:12][CH:13]=2)[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 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 711366701-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-[2-(methylsulfonyl)-1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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, 40 mg, 0.11 mmol, 1.0 equiv) was added to anhydrous acetonitrile (1.0 mL) followed by the sequential addition of DIPEA (55 μL, 0.31 mmol, 3.0 equiv) and methanesulfonyl chloride (12 μL, 0.16 mmol, 1.5 equiv). After 10 min at RT, LCMS showed complete consumption of starting material. Purification by reverse-phase HPLC (10-100% CH3CN:0.1% TFA in H2O) afforded 26-1 as a white solid. MS ink (M+H): calculated=461.1123; observed=461.1129.

Workup

  1. customconsumption of starting material
  2. customPurification by reverse-phase HPLC (10-100% CH3CN:0.1% TFA in H2O)

Sources & evidence

ORD record
ord-57977e56572341b8be2a1fb78808f062
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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