Hydrochloric Acid → (S)-N-(5-(Amino(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 530003Notes

Reaction equation

HRID 530003 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([C@H:21]([C:29]5[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=5[Cl:36])[NH:22][S@@](C(C)(C)C)=O)=[CH:19][N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.Cl.O1CCOCC1>CO>[NH2:22][C@@H:21]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=1[Cl:36])[C:18]1[S:17][C:16]([NH:15][C:13]([C:10]2([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)[CH2:11][CH2:12]2)=[O:14])=[N:20][CH:19]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 597571121-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl) thiazol-2-yl)cyclopropanecarboxamide

Product 1

HCID 59757103(S)-N-(5-(Amino(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution, of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-(2-chloro-4-fluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl)thiazol-2-yl)cyclopropanecarboxamide (659 mg, 1.2 mmol) in MeOH (5 mL) was added 4M HCl in dioxane (1.8 mL, 7.2 mmol). The reaction mixture was stirred at room temperature for 1.5 h and evaporated to dryness. The crude product was dissolved in CH2Cl2. The organic layer was washed with aqueous NaHCO3 solution (50 mL×2), brine (50 mL×1), dried over MgSO4 and concentrated to provide (S)-N-(5-(Amino(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide as a colorless solid that was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 8.48 (br s, 1H), 7.63 (dd, J=6.1, 8.7 Hz, 1H), 7.18 (s, 1H), 7.08 (dd, J=2.6, 8.4 Hz, 1H), 6.99 (td, J=8.3, 2.6 Hz, 1H), 6.91-6.86 (m, 2H), 6.81 (d, J=7.9 Hz, 1H), 6.01 (s, 2H), 5.78 (s, 1H), 3.80 (s, 2H), 1.74-1.67 (m, 2H), 1.30-1.22 (m, 2H); HPLC ret. time 2.67 min, 10-99% CH3CN, 5 min run: ESI-MS 446.3 m/z (MH+).

Workup

  1. customevaporated to dryness
  2. dissolutionThe crude product was dissolved in CH2Cl2
  3. washThe organic layer was washed with aqueous NaHCO3 solution (50 mL×2), brine (50 mL×1)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-927aecac19984ea9b04c80b0334d6fdf
Source dataset
uspto-grants-2016_05
Patent number
US09351962B2

Reaction notes

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