Hydrochloric Acid → HCID 24936846, compound

HRID 561035Notes

Reaction equation

HRID 561035 reaction equation
Cl.C(OC(=O)[N:8]([CH2:15][C:16]1[CH:17]=[N:18][C:19]([F:47])=[CH:20][C:21]=1[C:22]1[C:27]2[S:28][C:29]([C:31]3[C:36]([F:37])=[CH:35][N:34]=[C:33]([NH:38][CH2:39][CH2:40][N:41]4[CH2:45][CH2:44][NH:43][C:42]4=[O:46])[N:32]=3)=[CH:30][C:26]=2[CH:25]=[CH:24][CH:23]=1)[CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])(C)(C)C>ClCCl>[F:37][C:36]1[C:31]([C:29]2[S:28][C:27]3[C:22]([C:21]4[C:16]([CH2:15][NH:8][CH2:9][CH2:10][C:11]([F:12])([F:13])[F:14])=[CH:17][N:18]=[C:19]([F:47])[CH:20]=4)=[CH:23][CH:24]=[CH:25][C:26]=3[CH:30]=2)=[N:32][C:33]([NH:38][CH2:39][CH2:40][N:41]2[CH2:45][CH2:44][NH:43][C:42]2=[O:46])=[N:34][CH:35]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66998179HCID 66998179, compound

Product 1

HCID 24936846HCID 24936846, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add hydrogen chloride (2 mL, 1 M in diethyl ether) to a solution of [6-fluoro-4-(2-{5-fluoro-2-[2-(2-oxo-imidazolidin-1-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophen-7-yl)-pyridin-3-ylmethyl]-(3,3,3-trifluoro-propyl) carbamic acid tert-butyl ester (0.136 g, 200.68 μmol) in dichloromethane (3 mL). Stir the mixture overnight at room temperature. Evaporate the solvent and suspend the resulting solid in dichloromethane and treat with 30% aqueous potassium carbonate. Wash the organic phase with saturated aqueous sodium chloride and load the organic solution onto a 25 g silica gel loading column with dichloromethane and elute onto a 40 g silica gel column with a gradient from dichloromethane to ethyl acetate and then from ethyl acetate to 10% methanol in ethyl acetate to give the title compound. Purify the material further by HPLC (HPLC Conditions: 38-42% CH3CN/10 mM NH4HCO3, pH 10 at 20 mL/min on XBride® MS C18 19×100 mm) Collect the appropriate fractions and concentrate it. Co-evaporate the residue with two portions absolute ethanol, one portion toluene, and transfer to a 10 mL round bottom with dichloromethane. Convert the material to a solid using dichloromethane hexane co-evaporation to give the title compound 45 mg (39%) as a yellow solid. MS (ES) m/z 578 [M+1]+.

Workup

  1. customEvaporate the solvent
  2. additiontreat with 30% aqueous potassium carbonate
  3. washWash the organic phase with saturated aqueous sodium chloride and load the organic solution onto a 25 g silica gel loading column with dichloromethane
  4. washelute onto a 40 g silica gel column with a gradient from dichloromethane to ethyl acetate

Sources & evidence

ORD record
ord-d155dbe8284b4751b8fb315ff20eb037
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Reaction notes

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