Hydrochloric Acid → HCID 178447013, compound

HRID 2040722Notes

Reaction equation

HRID 2040722 reaction equation
[CH3:1][O:2][CH2:3][C:4]([C:7]1[CH:44]=[CH:43][C:10]2[NH:11][C:12]([CH2:14][CH2:15][CH:16]3[CH2:19][CH:18]([N:20]([CH2:22][C@@H:23]4[C@H:27]5[O:28]C(C)(C)[O:30][C@H:26]5[C@H:25]([N:33]5[CH:41]=[N:40][C:39]6[C:34]5=[N:35][CH:36]=[N:37][C:38]=6[NH2:42])[O:24]4)[CH3:21])[CH2:17]3)=[N:13][C:9]=2[CH:8]=1)([CH3:6])[CH3:5].Cl.[CH3:46]O>>[NH2:42][C:38]1[N:37]=[CH:36][N:35]=[C:34]2[C:39]=1[N:40]=[CH:41][N:33]2[C@H:25]1[C@H:26]([OH:30])[C@H:27]([OH:28])[C@@H:23]([CH2:22][N:20]([CH:18]2[CH2:19][CH:16]([CH2:15][CH2:14][C:12]3[NH:11][C:10]4[CH:43]=[CH:44][C:7]([C:4]([CH2:5][CH3:46])([CH3:6])[CH2:3][O:2][CH3:1])=[CH:8][C:9]=4[N:13]=3)[CH2:17]2)[CH3:21])[O:24]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 178494914HCID 178494914, compound

Product 1

HCID 178447013HCID 178447013, compoundYield 53%

Procedure

9-[(3aR,4R,6R,6aR)-6-{[(3-{2-[5-(1-Methoxy-2-methylpropan-2-yl)-1H-1,3-benzodiazol-2-yl]ethyl}cyclobutyl)(methyl)amino]methyl}-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine (0.485 g, 0.706 mmol, 88% pure) was dissolved in MeOH (20 ml) and cone. HCl (4.9 ml, 10 vol) was added at r.t. and the reaction left for 2.5 h. The reaction was concentrated in vacuo and the residue dissolved in the minimum amount of MeOH (˜2 ml). The reaction was quenched by addition of sat. NaHCO3 solution (10 ml) and EtOAc (30 ml). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 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 20% 2M NH3 in MeOH:80% DCM as eluent to give the product as a white foam (0.213 g, 53%): MS (ESI+) for C29H40N8O4 m/z 565.4[M+H]+; LC purity 100% (ret. time, 2.11 min) (7 min); 1H NMR (500 MHz, d4-MeOD) δH 8.28 (d, J=4.1 Hz, 1H), 8.22 (d, J=3.2 Hz, 1H), 7.51 (s, 1H), 7.42 (dd, J=8.5, 2.1 Hz, 1H), 7.29 (dd, J=8.5, 1.5 Hz, 1H), 6.01 (t, J=3.9 Hz, 1H), 4.84-4.74 (m, 1H), 4.41-4.29 (m, 1H), 4.29-4.19 (m, 1H), 3.48 (s, 2H), 3.30 (s, 3H), 3.14-2.98 (m, 1H), 2.99-2.89 (m, 1H), 2.90-2.73 (m, 2H), 2.39 (s, 3H), 2.37-2.30 (m, 1H), 2.28-2.10 (m, 2H), 2.08-1.86 (m, 4H), 1.70-1.51 (m, 1H), 1.38 (s, 6H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue dissolved in the minimum amount of MeOH (˜2 ml)
  3. customThe reaction was quenched by addition of sat. NaHCO3 solution (10 ml) and EtOAc (30 ml)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×30 ml)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product
  10. customThe product was purified by silica flash column chromatography

Sources & evidence

ORD record
ord-f420a4c05c4645c18462a5186129d5e5
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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