Trifluoroacetic acid → HCID 68858540, compound

HRID 1986189Notes

Reaction equation

HRID 1986189 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:18][NH:19][C:20]([C:22]1[CH:23]=[CH:24][C:25]2[CH:29]=[C:28]([C:30]3[C:35]([Cl:36])=[CH:34][N:33]=[C:32](Cl)[N:31]=3)[S:27][C:26]=2[CH:38]=1)=[O:21].C(N(C(C)C)CC)(C)C.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>O1CCOCC1.ClCCl>[CH3:18][NH:19][C:20]([C:22]1[CH:23]=[CH:24][C:25]2[CH:29]=[C:28]([C:30]3[C:35]([Cl:36])=[CH:34][N:33]=[C:32]([NH:17][CH2:16][CH2:15][CH2:14][CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[N:31]=3)[S:27][C:26]=2[CH:38]=1)=[O:21]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 22990164tert-Butyl 4-(3-aminopropyl)piperidine-1-carboxylateHCID 86625347HCID 86625347, compound

Product 1

HCID 68858540HCID 68858540, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

4-(3-Aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.72 g, 3.0 mmol) is added to a stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-6-carboxylic acid methylamide (0.40 g, 1.2 mmol) and diisopropylethylamine (0.38 g, 3.0 mmol) in anhydrous 1,4-dioxane (15 mL) at room temperature under nitrogen. The resultant mixture is heated in an oil bath at 90° C. for 12 hours. At room temperature, the mixture is concentrated and the resultant solid is washed with diethyl ether (20 mL) to give a yellow solid. The solid is suspended in dichloromethane (5 mL), followed by the successive addition of triethylsilane (0.7 mL) and TFA (4 mL). The resultant yellow solution is stirred for 2 hours. After concentration to dryness, the crude product is dissolved in MeOH (20 mL)/dichloromethane (10 mL) and the solution is treated in portions with 2N LiOH (4.2 mL) to form a suspension. After concentration and subsequent chromatography on silica gel, eluting with 2.0 M NH3/MeOH in dichloromethane 0-10%, the title compound is obtained as a yellow solid (0.26 g, yield 49%). ES+(m/z) 444 (35Cl) and 446 (37Cl) [M+H].

Workup

  1. concentrationAt room temperature, the mixture is concentrated
  2. washthe resultant solid is washed with diethyl ether (20 mL)
  3. customto give a yellow solid
  4. concentrationAfter concentration to dryness
  5. dissolutionthe crude product is dissolved in MeOH (20 mL)/dichloromethane (10 mL)
  6. additionthe solution is treated in portions with 2N LiOH (4.2 mL)
  7. customto form a suspension
  8. concentrationAfter concentration and subsequent chromatography on silica gel
  9. washeluting with 2.0 M NH3/MeOH in dichloromethane 0-10%

Sources & evidence

ORD record
ord-dddaeb6dfa034315b8518ad14f2287f2
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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