Pyridine → HCID 24967721, compound

HRID 222169Notes

Reaction equation

HRID 222169 reaction equation
[C@@H:1]1([NH:10][C:11]2[C:12]3[CH:19]=[CH:18][N:17]([C@H:20]4[C@@H:24]5[O:25]C(C)(C)[O:27][C@@H:23]5[C@H:22]([CH2:30][OH:31])[CH2:21]4)[C:13]=3[N:14]=[CH:15][N:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.N1C=CC=CC=1.Cl[S:39]([NH2:42])(=[O:41])=[O:40]>C(C#N)(C)=O.C(Cl)Cl>[S:39](=[O:41])(=[O:40])([O:31][CH2:30][C@@H:22]1[CH2:21][C@@H:20]([N:17]2[C:13]3[N:14]=[CH:15][N:16]=[C:11]([NH:10][C@@H:1]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH2:3][CH2:2]4)[C:12]=3[CH:19]=[CH:18]2)[C@H:24]([OH:25])[C@@H:23]1[OH:27])[NH2:42]

Participants

6

Reactant 3

HCID 1049PyridineHCID 24499Chlorosulfamic acid2×HCID 66618278((3aR,4S,6R,6aS)-6-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]-pyrimidin-7-yl}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Product 1

HCID 24967721HCID 24967721, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 694302-OxopropiononitrileSolvent3×

Procedure

To a suspension of ((3aR,4S,6R,6aS)-6-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]-dioxol-4-yl)methanol (45.9 mg, 0.109 mmol) and pyridine (0.0180 mL, 0.222 mmol) in AcCN (1.10 mL) and DCM (0.500 mL) at 0° C. under an atmosphere of nitrogen was added dropwise a 2.00 M solution of chlorosulfonamide in AcCN (0.110 mL, 0.220 mmol, as prepared in 1j). The suspension was stirred for 2 h and more 2.00 M of chlorosulfonamide in AcCN solution (0.150 mL, 3.00 mmol) was added. After 5 min the reaction was quenched with MeOH (1.00 mL) and the solvent was removed in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0 to 10% MeOH in DCM to afford the title compound as a white solid (23.1 mg, 46%). 1H NMR (400 MHz, CD3OD, δ): 8.36 (s, 1H), 7.62 (d, J=3.1 Hz, 1H), 7.43-7.33 (m, 4H), 7.04 (d, J=3.0 Hz, 1H), 5.67 (br s, 1H), 5.25-5.20 (m, 1H), 4.61 (dd, J=3.8, 9.3 Hz, 1H), 4.48 (dd, J=2.0, 9.9 Hz, 1H), 4.27-4.22 (m, 2H), 3.74 (s, 1H), 3.27-3.20 (m, 1H), 3.13-3.05 (m, 1H), 3.02-2.90 (m, 1H), 2.87-2.77 (m, 1H), 2.35-2.19 (m, 3H) ppm. LC/MS: Rt=0.94 min, ES+ 460. (FA standard).

Workup

  1. customAfter 5 min the reaction was quenched with MeOH (1.00 mL)
  2. customthe solvent was removed in vacuo
  3. customThe residue was purified by silica gel chromatography
  4. washeluting with a gradient of 0 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-58b7cecb603e4662b1789aad1c8ab1b9
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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