Hydrochloric Acid → HCID 178493503, compound

HRID 1778670Notes

Reaction equation

HRID 1778670 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]4)[C:16]2=[CH:15][N:14]=1.Cl.C(Cl)(=O)C.C(N(CC)C(C)C)(C)C.[CH3:53][S:54](Cl)(=[O:56])=[O:55]>CO>[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[CH2:28][N:27]([S:54]([CH3:53])(=[O:56])=[O:55])[CH2:26][CH2:25]4)[C:16]2=[CH:15][N:14]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178493502tert-butyl 6-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 178493503HCID 178493503, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

tert-Butyl 6-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate (10.0 mg, 0.0191 mmol) in methanol (0.10 mL) was treated at r.t. with HCl solution previously prepared from acetyl chloride (0.1 mL) and methanol (0.1 mL) at 0° C. The mixture was stirred at r.t. for 1 h. The volatiles were evaporated. The residue was dissolved in acetonitrile (0.5 mL) and N,N-diisopropylethylamine (30.0 μL, 0.172 mmol). To the mixture was added methanesulfonyl chloride (2.0 μL, 0.026 mmol). The mixture was stirred at r.t. for 1 h. The volatiles were removed. The residue was dissolved in methanol (0.5 mL) and treated with sodium methoxide (25%, 0.060 mL). After 1 h, the mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=502.1. 1H NMR (300 MHz, DMSO-d6) δ: 9.39 (s, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.89 (s, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.07 (t, J=8.1 Hz, 1H), 4.40 (s, 2H), 3.92 (s, 6H), 3.48 (t, J=5.7 Hz, 2H), 3.04 (d, J=5.7 Hz, 3H), 2.97 (s, 3H).

Workup

  1. customThe volatiles were evaporated
  2. dissolutionThe residue was dissolved in acetonitrile (0.5 mL)
  3. stirringThe mixture was stirred at r.t. for 1 h
  4. customThe volatiles were removed
  5. dissolutionThe residue was dissolved in methanol (0.5 mL)
  6. additiontreated with sodium methoxide (25%, 0.060 mL)
  7. waitAfter 1 h
  8. additionthe mixture was diluted with methanol
  9. custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-5ce24b2df84444609934a8d489e94425
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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