Hydrochloride methanol → Ammonia

HRID 1054542Notes

Reaction equation

HRID 1054542 reaction equation
[ClH:1].CO.[Cl:4][C:5]1[C:6]([C:54]([F:57])([F:56])[F:55])=[CH:7][C:8]2[N:12]=[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH2:21][C@@H:22]3[C@H:26]4[O:27]C(C)(C)[O:29][C@H:25]4[C@H:24]([N:32]4[C:36]5[N:37]=[CH:38][N:39]=[C:40]([NH:41][CH:42]6[CH2:44][CH2:43]6)[C:35]=5[CH:34]=[CH:33]4)[CH2:23]3)[CH:18]([CH3:20])[CH3:19])[N:10](COCC[Si](C)(C)C)[C:9]=2[CH:53]=1>>[NH3:10].[ClH:4].[ClH:1].[ClH:4].[Cl:4][C:5]1[C:6]([C:54]([F:57])([F:55])[F:56])=[CH:7][C:8]2[N:12]=[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH2:21][C@H:22]3[CH2:23][C@@H:24]([N:32]4[C:36]5[N:37]=[CH:38][N:39]=[C:40]([NH:41][CH:42]6[CH2:43][CH2:44]6)[C:35]=5[CH:34]=[CH:33]4)[C@H:25]([OH:29])[C@@H:26]3[OH:27])[CH:18]([CH3:20])[CH3:19])[NH:10][C:9]=2[CH:53]=1

Participants

4

Reactant 2

HCID 21893726Hydrochloride methanolHCID 67816584HCID 67816584, compound

Product 2

HCID 222AmmoniaHCID 178457188HCID 178457188, compound

Conditions

Temperature
40 °C

Procedure

A solution of 12N aq. HCl:MeOH (1:1, 3 ml) was added to 7-[(3aS,4R,6R,6aR)-6-[({4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)-ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl}(propan-2-yl)amino)methyl]-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine at 0° C., stirred at 40° C. for 4 hrs. Upon completion, the reaction mixture was concentrated in vacuo. The residue was dissolve in DCM (100 ml) and MeOH (1 ml). This was washed with sat. NaHCO3 (2×50 ml), dried over Na2SO4, filtered and evaporated. Purification by prep.TLC, eluting with MeOH:DCM (1:9) and then 7N NH3 in MeOH:DCM (5:95) gave the desired product. This was then dissolved in MeOH (1 ml). To this was added HCl (4M in dioxane, 5 eq), shaken for 5 mins and evaporated to dryness. This was then re-dissolved in Water (1 ml) and MeOH (3 drops) and lyophilised to give an off white solid (100 mg, 55%); MS (ESI+) for C30H37ClF3N7O2 m/z 620 [M+H]+: HPLC purity>95% (ret. time, 1.35 min): 1H NMR (500 MHz, MeOD) δ ppm 8.31 (1H, s), 8.16 (1H, s), 8.01 (1H, br. s.), 7.59 (1H, d, J=3.31 Hz), 6.91 (1H, br. s.), 5.08 (1H, br. s.), 4.30 (1H, t, J=5.91 Hz), 4.16 (1H, br. s.), 3.85 (1H, br. s.), 3.38-3.59 (2H, m), 2.85 (1H, br. s.), 2.52 (2H, br. s.), 1.93-2.21 (4H, m), 1.86 (1H, s), 1.32-1.52 (6H, m), 1.00-1.24 (2H, m), 0.73-1.00 (2H, m).

Workup

  1. concentrationUpon completion, the reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolve in DCM (100 ml)
  3. washThis was washed with sat. NaHCO3 (2×50 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by prep.TLC,
  8. washeluting with MeOH:DCM (1:9)

Sources & evidence

ORD record
ord-db6245c86b4240f494d6e9ffbe1785ba
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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