Trifluoroacetic acid → [(1R,2S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2-hydroxycyclopentyl]methyl sulfamate

HRID 1677926Notes

Reaction equation

HRID 1677926 reaction equation
[C@@H:1]1([NH:10][C:11]2[N:16]=[CH:15][N:14]=[C:13]([NH:17][C@@H:18]3[CH2:22][C@H:21]([CH2:23][O:24][S:25]([NH:28]C(=O)OC(C)(C)C)(=[O:27])=[O:26])[C@@H:20]([OH:36])[CH2:19]3)[CH:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>C(Cl)Cl>[S:25](=[O:27])(=[O:26])([O:24][CH2:23][C@H:21]1[CH2:22][C@@H:18]([NH:17][C:13]2[CH:12]=[C:11]([NH:10][C@@H:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][CH2:2]3)[N:16]=[CH:15][N:14]=2)[CH2:19][C@@H:20]1[OH:36])[NH2:28]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86618704tert-butyl ({[(1R,2S,4R)-4-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2-hydroxycyclopentyl]methoxy}sulfonyl)carbamate

Product 1

HCID 24829705[(1R,2S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2-hydroxycyclopentyl]methyl sulfamateYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ({[(1R,2S,4R)-4-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2-hydroxycyclopentyl]methoxy}sulfonyl)carbamate (50.0 mg, 0.0962 mmol) in DCM (2.00 mL) was added trifluoroacetic acid (0.500 mL, 6.49 mmol), and the mixture was stirred for 30 min. The mixture was concentrated in vacuo and the residue was purified via silica gel chromatography eluting with 10% MeOH in DCM, and the product was dissolved in MeOH and treated with solid NaHCO3. The suspension was filtered and the filtrate was purified via silica gel chromatography eluting with 10% MeOH/DCM to afford the title compound as an amorphous solid (12.0 mg, 30%). 1H NMR (CD3OD, 400 MHz) δ: 7.94 (s, 1H), 7.29-7.12 (m, 4H), 5.53 (s, 1H), 5.32 (bs, 1H), 4.23-4.08 (m, 4H), 3.06-2.96 (m, 1H), 2.93-2.82 (m, 1H), 2.61-2.50 (m, 1H), 2.45-2.34 (m, 1H), 2.26-2.15 (m, 1H), 2.08-1.98 (m, 1H), 1.95-1.78 (m, 2H), 1.37-1.25 (m, 2H) ppm. LC/MS: Rt=1.29 min, ES+ 420. (AA standard).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was purified via silica gel chromatography
  3. washeluting with 10% MeOH in DCM
  4. dissolutionthe product was dissolved in MeOH
  5. additiontreated with solid NaHCO3
  6. filtrationThe suspension was filtered
  7. customthe filtrate was purified via silica gel chromatography
  8. washeluting with 10% MeOH/DCM

Sources & evidence

ORD record
ord-216040fc16f44d07a36bd73b25e2c272
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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