Trifluoroacetic acid → HCID 20746015, compound

HRID 2308105Notes

Reaction equation

HRID 2308105 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]([N:26]5[CH2:30][CH:29]([O:31][CH3:32])[CH2:28][CH:27]5[C:33](C)(C)[O:34][SiH2]C(C)(C)C)=[O:25])[S:23][C:16]=34)=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:42])=[O:4].C(O)(C(F)(F)F)=O>C(O)(=O)C.C1COCC1>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]([N:26]5[CH2:30][CH:29]([O:31][CH3:32])[CH2:28][CH:27]5[CH2:33][OH:34])=[O:25])[S:23][C:16]=34)=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:42])=[O:4]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131724695HCID 131724695, compound

Product 1

HCID 20746015HCID 20746015, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Example 3(o) was prepared by dissolving the starting material 5-{2-[2-(tert -Butyl-dimethyl-silanyloxymethyl)-4-methoxy-pyrrolidine-1-carbonyl]-thieno[3,2-b]pyridin-7-yloxy}-2-methyl-indole-1-carboxylic acid methylamide (0.55 g, 1.00 mmol), as prepared in step i below, in 1 mL of acetic acid in 0.5 mL of THF and 0.5 mL of TFA and stirring at 50° C. for 3 h. The reaction mixture was quenched with 5 mL of sat. NaHCO3 and 50 mL of EtOAc the partitioned with 50/50 NaHCO3 (2×50 mL) organic layer dried over NaSO4 and concentrated. The residue purified with a 2 mm choromatotron rotor eluting with EtOAc/CH2Cl2/MeOH (2:1:0.2) then combining purified fractions. The product was then crashing out of EtOAc and diethyl ether producing 0.34 g (68.5%) of 5-[2-(2-Hydroxymethyl-4-methoxy-pyrrolidine-1-carbonyl)-thieno[3,2-b]pyridin-7-yloxy]-2-methyl-indole-1-carboxylic acid methylamide as white solid. HPLC: Rt 5.06 min. (94% area). 1H NMR (CDCl3, 400 MHz) δ: 8.50 (1H, d, J=5.3 Hz), 7.81 (1H, s), 7.71 (1H, d, J=9.0), 7.30 (1H, s), 7.03 (1H, d, J=6.9 Hz), 6.60 (1H, d, J=5.3 Hz), 6.33 (1H, s), 5.69 (1H, bs), 4.57 (1H, q, J=6.8 Hz), 4.33 (1H, s), 4.08 (1H, d, J=11.6 Hz), 4.00 (1H, s), 3.86 (2H, t, J=11.6 Hz), 3.85-3.75 (1H, m), 3.28 (3H, d, J=4.3 Hz), 2.61 (3H, s), 2.34-2.29 (1H, m). HRMS (ESI) C25H27N4O5S2 (M+H+) m/z: Calc. 495.1702, Found: 495.1704. Anal. (C25H26N4O5S2.0.2 EtOAc) Calc'd: C, 60.50; H, 5.43; N, 10.94; Found: C, 60.73; H, 5.61; N, 10.10.86.

Workup

  1. customExample 3(o) was prepared
  2. customThe reaction mixture was quenched with 5 mL of sat. NaHCO3 and 50 mL of EtOAc the
  3. custompartitioned with 50/50 NaHCO3 (2×50 mL) organic layer
  4. dry with materialdried over NaSO4
  5. concentrationconcentrated
  6. customThe residue purified with a 2 mm choromatotron rotor
  7. washeluting with EtOAc/CH2Cl2/MeOH (2:1:0.2)
  8. customthen combining purified fractions

Sources & evidence

ORD record
ord-eaaf83d35ed141abac74c61769f310c5
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

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