Ammonia → (3R)-3-(6-Benzo[b]thiophen-5-yl-pyridazin-3-yloxy)-1-aza-bicyclo[2.2.2]octane trifluoroacetate

HRID 1441444Notes

Reaction equation

HRID 1441444 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][C@@H:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[CH:4][CH:3]=1.[S:17]1[C:21]2[CH:22]=[CH:23][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:25][C:20]=2[CH:19]=[CH:18]1.N.[C:36]([C:40]([OH:42])=[O:41])([F:39])([F:38])[F:37]>>[F:37][C:36]([F:39])([F:38])[C:40]([OH:42])=[O:41].[S:17]1[CH:18]=[CH:19][C:20]2[CH:25]=[C:24]([C:2]3[N:7]=[N:6][C:5]([O:8][C@@H:9]4[CH:14]5[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]5)[CH2:10]4)=[CH:4][CH:3]=3)[CH:23]=[CH:22][C:21]1=2

Participants

5

Reactant 4

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 27954552-(1-Benzothiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86598842(3R)-3-[(6-chloropyridazin-3-yl)oxy]quinuclidine

Product 1

HCID 68543240(3R)-3-(6-Benzo[b]thiophen-5-yl-pyridazin-3-yloxy)-1-aza-bicyclo[2.2.2]octane trifluoroacetate

Procedure

The product of Example 9A (120 mg, 0.5 mmol) was coupled with 2-(1-benzothiophen-5-yl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Maybridge, 260 mg, 1.0 mmol) according to the procedure of Example 26B. The title product was purified by preparative HPLC (column: Xterra™ RP-18, 5 μm, 30×100 mm. eluting solvent, MeCN/H2O (with 0.1% v. TFA), (v. 90/10 to 10/90 over 20 min.) flow rate, 40 mL/min., uv, 254 nm) to provide a solid (157.3 mg, yield, 70%). 1H NMR (300 MHz, CD3OD) δ 1.92-2.25 (m, 3H) 2.35-2.49 (m, 1H) 2.63-2.71 (m, 1H) 3.35-3.56 (m, 5H) 3.95-4.06 (m, 1H) 5.55-5.62 (m, 1H) 7.37 (d, J=9.16 Hz, 1H) 7.50 (dd, J=5.43, 0.68 Hz, 1H) 7.68 (d, J=5.43 Hz, 1H) 7.96-8.02 (m, 1H) 8.05-8.10 (m, 1H) 8.22 (d, J=9.49 Hz, 1H) 8.45 (d, J=1.70 Hz, 1H) ppm. MS (DCI/NH3) m/z 338 (M+H)+. Anal. Calculated for C19H19N3OS.CF3CO2H: C, 55.87; H, 4.47; N, 9.31. Found: C, 55.51; H, 4.28; N, 9.12.

Workup

  1. customThe title product was purified by preparative HPLC (column: Xterra™ RP-18, 5 μm, 30×100 mm. eluting solvent, MeCN/H2O (with 0.1% v. TFA), (v. 90/10 to 10/90 over 20 min.) flow rate, 40 mL/min., uv, 254 nm)
  2. customto provide
  3. customa solid (157.3 mg, yield, 70%)

Sources & evidence

ORD record
ord-c71b78ed543044cdb2712010efded072
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

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