Hydrochloric Acid → HCID 178514806, compound

HRID 1747579Notes

Reaction equation

HRID 1747579 reaction equation
CC1(C)[O:6][C@H:5]2[C@H:7]([NH:12][C:13]3[N:21]=[CH:20][N:19]=[C:18]4[C:14]=3[N:15]=[CH:16][NH:17]4)[CH2:8][C@H:9]([CH2:10][OH:11])[C@H:4]2[O:3]1.CCN(CC)CC.Cl[S:31]([NH2:34])(=[O:33])=[O:32].C(#N)C.Cl.O>C(Cl)Cl.CN(C=O)C>[S:31](=[O:33])(=[O:32])([O:11][CH2:10][C@H:9]1[CH2:8][C@@H:7]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[C@H:5]([OH:6])[C@@H:4]1[OH:3])[NH2:34]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 6342AcetonitrileHCID 8471TriethylamineHCID 24499Chlorosulfamic acidHCID 178431643HCID 178431643, compound

Product 1

HCID 178514806HCID 178514806, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of [(3aR,4R,6R,6aS)-2,2-dimethyl-6-(9H-purin-6-ylamino)tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol (288 mg, 0.943 mmol) and Et3N (0.400 mL, 2.87 mmol) in DCM (5.00 mL) was cooled to 0° C. A 2.00 M solution of chlorosulfonamide in ACN (0.94 mL, 1.88 mmol, as prepared in Example 1d) was added dropwise, and DMF (1.50 mL) was added to bring the mixture into solution. The solution was allowed to warm to 23° C. and was stirred for 5 h before being concentrated in vacuo to dryness. The crude mixture was treated with a 1.00 M solution of HCl in H2O (5.00 mL, 5.00 mmol) and stirred for 10 min. The mixture was concentrated to dryness and purified via reverse phase C18 preparative HPLC eluting with a gradient of 0 to 40% of 0.1% FA/95% ACN/5% H2O in 0.1% FA/99% H2O/1% ACN over 16 min to afford the title compound (95.0 mg, 29%). 1H NMR (DMSO-d6, 400 MHz) δ: 12.9 (bs, 1H), 8.25-8.01 (m, 2H), 7.68-7.29 (m, 3H), 5.12-4.30 (m, 3H), 4.10 (dd, J=5.8, 9.6 Hz, 1H), 4.01 (dd, J=7.0, 9.6 Hz, 1H), 3.85 (dd, J=5.6, 5.6, 1H), 3.75 (dd, J=5.2, 5.2 Hz, 1H), 2.35-2.13 (m, 2H), 1.33-1.19 (m, 1H) ppm. LC/MS: Rt=1.02 min, ES+ 345 (AA standard).

Workup

  1. temperatureto warm to 23° C.
  2. concentrationbefore being concentrated in vacuo to dryness
  3. stirringstirred for 10 min
  4. concentrationThe mixture was concentrated to dryness
  5. custompurified via reverse phase C18 preparative HPLC
  6. washeluting with a gradient of 0 to 40% of 0.1%
  7. customover 16 min

Sources & evidence

ORD record
ord-30940bf7fe1c46958f6165eb1b9e910e
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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