Acetone → 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1054528Notes

Reaction equation

HRID 1054528 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:7]2[O:8][C:9]([CH3:12])([CH3:11])[O:10][C@H:6]2[C@H:5]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH2:22])[C:16]=3[CH:15]=[CH:14]2)[CH2:4]1.[CH3:23][C:24](=O)[CH3:25].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:11][C:9]1([CH3:12])[O:8][C@@H:7]2[C@@H:3]([CH2:2][NH:1][CH:24]([CH3:25])[CH3:23])[CH2:4][C@@H:5]([N:13]3[C:17]4[N:18]=[CH:19][N:20]=[C:21]([NH2:22])[C:16]=4[CH:15]=[CH:14]3)[C@@H:6]2[O:10]1

Participants

5

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 678180027-[(3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethylhexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 677763337-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 81%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

7-[(3aS,4R,6R,6aR)-6-(Aminomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1.024 g, 3.38 mmol) was dissolved in DCE (35 ml) and propan-2-one (0.50 ml, 6.75 mmol) was added and the reaction left for 15 mins. Sodium triacetoxyborohydride (1.002 g, 4.73 mmol) was added and the reaction left overnight. The reaction was quenched by the addition of sat. Na2CO3 solution (35 ml) and DCM (35 ml). The organic layer was separated and the aqueous layer was extracted with DCM (3×35 ml). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% DCM and 15% 2M NH3 in MeOH:85% DCM as eluent to give the product as a white foamy solid (0.941 g, 81%): MS (ESI+) for C18H27N5O2 m/z 346.1 [M+H]+, 368.1 [m+Na]+; LCMS: Compound in solvent front; 1H NMR (500 MHz, CDCl3) δ 8.32 (s, 1H), 7.04 (d, J=3.63 Hz, 1H), 6.36 (d, J=3.47 Hz, 1H), 5.08 (br. s., 2H), 4.87-5.02 (m, 2H), 4.54 (t, J=6.38 Hz, 1H), 2.80-2.90 (m, 2H), 2.70-2.80 (m, 1H), 2.46 (dt, J=12.77, 6.54 Hz, 1H), 2.30-2.37 (m, 1H), 2.17 (q, J=11.98 Hz, 1H), 1.57 (s, 3H), 1.31 (s, 3H), 1.09 (t, J=5.44 Hz, 6H).

Workup

  1. waitthe reaction left overnight
  2. customThe reaction was quenched by the addition of sat. Na2CO3 solution (35 ml) and DCM (35 ml)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM (3×35 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customThe product was purified by silica flash column chromatography

Sources & evidence

ORD record
ord-6a3bd5e9dec4402280b1be5b534dca59
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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