Hydrochloric Acid → HCID 25121260, compound

HRID 1640934Notes

Reaction equation

HRID 1640934 reaction equation
[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:24]5[CH:29]=[C:28]([F:30])[N:27]=[CH:26][C:25]=5[CH2:31][N:32]5[CH2:36][CH2:35][CH:34]([N:37](C)[C:38](=O)OC(C)(C)C)[CH2:33]5)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:46])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1.Cl.O1CCOCC1>C(Cl)Cl.CO>[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:24]5[C:25]([CH2:31][N:32]6[CH2:36][CH2:35][CH:34]([NH:37][CH3:38])[CH2:33]6)=[CH:26][N:27]=[C:28]([F:30])[CH:29]=5)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:46])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66738377HCID 66738377, compound

Product 1

HCID 25121260HCID 25121260, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
35 °C

Procedure

Dilute tert-butyl 1-((4-(2-(2-(2-(1H-1,2,3-triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)-6-fluoropyridin-3-yl)methyl)pyrrolidin-3-yl(methyl)carbamate (118 mg, 0.18 mmol) in DCM (3 mL) and treat with 4 M hydrochloric acid in dioxane (0.45 mL, 1.8 mmol). Heat the mixture at 35° C. for 2 h. Remove the organic solvent to give the crude deprotected product. Dilute in DCM (3 mL) and methanol. Pour the mixture onto a strong cation exchange (SCX) (10 g) column. Elute the desired product with 2 N methanolic ammonia (40 mL) and concentrate. Dry the concentrated material from 1:1 acetonitrile/water by lyophilizing to afford the title compound (88 mg, 46%). MS (ES) m/z 548 [M+1]+.

Workup

  1. customRemove the organic solvent
  2. customto give the crude deprotected product
  3. additionPour the mixture onto a strong cation exchange (SCX) (10 g) column
  4. washElute the desired product with 2 N methanolic ammonia (40 mL)
  5. concentrationconcentrate
  6. dry with materialDry the concentrated material from 1:1 acetonitrile/water

Sources & evidence

ORD record
ord-27bfb9ac7a134574b7d8749e312acf76
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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