1,2-Dichloroethane → (2S)-1-[5-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-3,3a,4,6a-tetrahydrocyclopenta-[c]pyrrol-2(1H)-yl]-3,3,3-trifluoro-2-hydroxypropan-1-one

HRID 629895Notes

Reaction equation

HRID 629895 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].[F:27][C:28]([F:35])([F:34])[C@@H:29]([OH:33])[C:30](O)=[O:31].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)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]([C:30](=[O:31])[C@H:29]([OH:33])[C:28]([F:35])([F:34])[F:27])[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

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 7457723(2S)-3,3,3-trifluoro-2-hydroxypropanoic acidHCID 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 117702433(2S)-1-[5-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-3,3a,4,6a-tetrahydrocyclopenta-[c]pyrrol-2(1H)-yl]-3,3,3-trifluoro-2-hydroxypropan-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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, 0.79 g, 2.1 mmol, 1.0 equiv), (2S)-3,3,3-trifluoro-2-hydroxypropanoic acid (24-3, 0.30 g, 2.1 mmol, 1.0 equiv), EDC (0.40 g, 2.1 mmol, 1.0 equiv), HOBT (0.32 g, 2.1 mmol, 1.0 equiv) and triethylamine (0.58 mL, 4.2 mmol, 2.0 equiv) were added to anhydrous DMF (13.6 mL) and stirred at RT. After 18 h, the contents were partitioned between ethyl acetate (50 mL) and saturated NaHCO3 (20 mL). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (2×20 mL). The combined organics were washed with H2O (5×20 mL), dried over Na2SO4, filtered and concentrated in vacuo to give a dark red oil. Purification by normal-phase chromatography (0-60% EtOAc:Hex) afforded 24-4 as a white solid. MS m/z (M+H): calculated=509.1276; observed=509.1281.

Workup

  1. customthe contents were partitioned between ethyl acetate (50 mL) and saturated NaHCO3 (20 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was back-extracted with ethyl acetate (2×20 mL)
  4. washThe combined organics were washed with H2O (5×20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a dark red oil
  9. customPurification by normal-phase chromatography (0-60% EtOAc:Hex)

Sources & evidence

ORD record
ord-0581a8b2829445b2a2e9ea5d2bad189f
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

Loading…