Hydrochloric Acid → HCID 86705760, compound

HRID 1054548Notes

Reaction equation

HRID 1054548 reaction equation
CC1(C)[O:6][C@@H:5]2[C@@H:7]([CH2:23][N:24]([CH:50]([CH3:52])[CH3:51])[CH2:25][CH2:26][CH2:27][CH2:28][C:29]3[N:33](COCC[Si](C)(C)C)[C:32]4[CH:42]=[C:43]([C:46]([F:49])([F:48])[F:47])[CH:44]=[CH:45][C:31]=4[N:30]=3)[CH2:8][C@@H:9]([N:10]3[C:14]4[N:15]=[CH:16][N:17]=[C:18]([NH:19][CH:20]5[CH2:22][CH2:21]5)[C:13]=4[CH:12]=[CH:11]3)[C@@H:4]2[O:3]1.[ClH:54]>CO>[ClH:54].[ClH:54].[ClH:54].[CH:20]1([NH:19][C:18]2[C:13]3[CH:12]=[CH:11][N:10]([C@@H:9]4[CH2:8][C@H:7]([CH2:23][N:24]([CH:50]([CH3:51])[CH3:52])[CH2:25][CH2:26][CH2:27][CH2:28][C:29]5[NH:33][C:32]6[CH:42]=[C:43]([C:46]([F:49])([F:48])[F:47])[CH:44]=[CH:45][C:31]=6[N:30]=5)[C@@H:5]([OH:6])[C@H:4]4[OH:3])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH2:21][CH2:22]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67816262HCID 67816262, compound

Product 1

HCID 86705760HCID 86705760, compoundYield 29.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-{[propan-2-yl({4-[6-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl})amino]methyl}-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (199 mg) was dissolved in methanol (2 ml), and conc. HCl solution (2 ml) was slowly added. The reaction was heated to 40° C. and stirred at this temperature for 5 h. The reaction mixture was concentrated under reduced pressure, and the residue partitioned between sat. NaHCO3(aq) (10 ml) and EtOAc (10 ml). A small amount of MeOH (−1 ml) was added to aid dissolution, and the layers were separated. The aqueous layer was extracted with EtOAc (2×10 ml), the combined organics were then dried (Na2SO4) and concentrated. The crude material was purified by preparative TLC, eluting twice with 7.5% 2M NH3 in MeOH in DCM to afford 48.2 mg (29.6%) of the free base of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue partitioned between sat. NaHCO3(aq) (10 ml) and EtOAc (10 ml)
  3. additionA small amount of MeOH (−1 ml) was added to aid dissolution
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 ml)
  6. dry with materialthe combined organics were then dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude material was purified by preparative TLC
  9. washeluting twice with 7.5% 2M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-17e3a7374bbe49caa5dca5c1bdf98334
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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