Pyridine → HCID 66892783, compound

HRID 1162022Notes

Reaction equation

HRID 1162022 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([Cl:12])(=[O:11])=[O:10].[N:15]1C=CC=CC=1.C(OC(=O)N[CH:28]1[CH2:33][CH2:32][N:31]([C:34]2[C:42]3[O:41][CH:40]=[CH:39][C:38]=3[CH:37]=[C:36]([NH2:43])[CH:35]=2)[CH2:30][CH2:29]1)(C)(C)C>C(Cl)Cl>[ClH:12].[NH2:15][CH:32]1[CH2:33][CH2:28][CH2:29][CH2:30][N:31]1[C:34]1[C:42]2[O:41][CH:40]=[CH:39][C:38]=2[CH:37]=[C:36]([NH:43][S:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:2]([F:14])([F:13])[F:1])(=[O:11])=[O:10])[CH:35]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 1366162-Trifluoromethylbenzenesulphonyl chlorideHCID 86609637HCID 86609637, compound2×

Product 1

HCID 66892783HCID 66892783, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(Trifluoromethyl)benzenesulfonyl chloride (89.0 mg, 0.36 mmol) and pyridine (219 mL) were added to tert-butyl[1-(5-amino-1-benzofuran-7-yl)piperidin-4-yl]carbamate (100.0 mg, 0.30 mmol; Intermediate 49) in DCM (1 mL). The mixture was shaken at room temperature for 1 h, solvent removed in vacuo and the residue was purified by preparative HPLC using acetonitrile-water gradients containing 0.1% trifluoroacetic acid. N-deprotection and conversion into the hydrochloride salt was performed by treatment with 2 M HCl in ether. This furnished 76.1 mg (57%) of the title product. HPLC 100%, RT: 1.834 (System A; 10-97% MeCN over 3 min). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.70-1.72 (m, 2H) 2.00-2.02 (m, 2H) 2.78 (t, J=11.30 Hz, 2H) 3.21 (s, 1H) 3.71 (d, J=12.56 Hz, 2H) 6.60 (d, J=1.88 Hz, 1H) 6.83 (d, J=2.20 Hz, 1H) 6.85-6.91 (m, J=1.88 Hz, 1H) 7.80-7.81 (m, 2H) 7.88-7.89 (m, 1H) 7.96-7.98 (m, 1H) 8.08-8.10 (m, 4H) 10.40 (s, 1H). LC-MS 440 (M+H)+.

Workup

  1. customsolvent removed in vacuo
  2. customthe residue was purified by preparative HPLC
  3. additioncontaining 0.1% trifluoroacetic acid
  4. customHPLC 100%, RT
  5. wait10-97% MeCN over 3 min)

Sources & evidence

ORD record
ord-76ed6156b25b40bcaef194c77a84664a
Source dataset
uspto-grants-2010_10
Patent number
US07820675B2

Reaction notes

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