Hydrochloric Acid → HCID 59757107, compound

HRID 529988Notes

Reaction equation

HRID 529988 reaction equation
C([S@@]([NH:7][C@H:8]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[C:9]1[S:13][C:12]([NH:14][C:15]([C:17]2([C:20]3[CH:28]=[CH:27][C:23]4[O:24][CH2:25][O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]2)=[O:16])=[N:11][CH:10]=1)=O)(C)(C)C.Cl.O1CCOCC1>CO>[NH2:7][C@@H:8]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35])[C:9]1[S:13][C:12]([NH:14][C:15]([C:17]2([C:20]3[CH:28]=[CH:27][C:23]4[O:24][CH2:25][O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]2)=[O:16])=[N:11][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86621210(S)-N-(5-((R)-t-butylsulfinylamino(2-chlorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Product 1

HCID 59757107HCID 59757107, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (S)-N-(5-((R)-t-butylsulfinylamino-(2-chlorophenyl)-methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropane-carboxamide (11.25 g, 21.19 mmol) in MeOH (100 mL) was added 4 M HCl in dioxane (32 mL, 128 mmol). The reaction mixture was stirred at 25° C. for 1.5 h and evaporated to dryness. The crude product was dissolved in CH2Cl2. The organic layer was washed with aqueous NaHCO3(50 mL×2), brine (50 mL×1), dried over Na2SO4 and concentrated. The crude product was purified by column chromatography (0-2.5% Et3N-EtOAc) to provide (S)-N-(5-(amino(2-chlorophenyl)-methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (6.5 g, 72%, >99% ee). 1H-NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.60 (dd, J=7.7, 1.7 Hz, 1H), 7.33 (dd, J=7.9, 1.3 Hz, 1H), 7.29-7.25 (m, 1H), 7.20 (td, J=7.6, 1.7 Hz, 1H), 7.16 (d, J=1.0 Hz, 1H), 6.89 (td, J=7.8, 1.7 Hz, 2H), 6.80 (d, J=7.9 Hz, 1H), 6.01 (s, 2H), 5.79 (s, 1H), 1.86 (bs, 2H), 1.72-1.69 (m, 2H), 1.22-1.19 (m, 2H). HPLC ret. time 2.66 min, 10-99% CH3CN, 5 min run; ESI-MS 428.1 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(50 mL×2), brine (50 mL×1)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (0-2.5% Et3N-EtOAc)

Sources & evidence

ORD record
ord-d7520230d08741ddadb078c0fc8cfbdf
Source dataset
uspto-grants-2016_05
Patent number
US09351962B2

Reaction notes

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