Trifluoroacetic acid → 1-(3-Fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-isopropylurea

HRID 409961Notes

Reaction equation

HRID 409961 reaction equation
C(OC(=O)[N:7]([CH2:12][C:13]1[N:17]([CH3:18])[C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH:38][CH:39]([CH3:41])[CH3:40])=[O:37])=[CH:31][C:30]=3[F:42])[CH:20]=2)=[N:15][CH:14]=1)[CH2:8][CH2:9][O:10][CH3:11])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:42][C:30]1[CH:31]=[C:32]([NH:35][C:36]([NH:38][CH:39]([CH3:41])[CH3:40])=[O:37])[CH:33]=[CH:34][C:29]=1[O:28][C:25]1[CH:24]=[CH:23][N:22]=[C:21]2[CH:20]=[C:19]([C:16]3[N:17]([CH3:18])[C:13]([CH2:12][NH:7][CH2:8][CH2:9][O:10][CH3:11])=[CH:14][N:15]=3)[S:27][C:26]=12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67048356tert-Butyl (2-(7-(2-fluoro-4-(3-isopropylureido)phenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

Product 1

HCID 441994461-(3-Fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-isopropylureaYield 55.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The solution of urea 314 (150 mg, 0.245 mmol) and TFA (1 mL, 12.98 mmol) in DCM (20 mL) was stirred 4 hr at room temperature and concentrated. The residue was partitioned between EtOAc/NaHCO3 sat. solution. The solid was collected by filtration and combined with organic layer. The mixture was concentrated and the residue was purified via Biotage (EA/MeOH 0-40%, 12 g Silicycle HR column). Collected fractions gave the desired product 315 (70 mg, 0.137 mmol, 55.8% yield) as a white solid. 1HNMR (dmso-d6) δ(ppm) 1H:8.67 (s, 1H), 8.48 (d, 1H, J=5.5 Hz), 7.91 (s, 1H), 7.65 (dd, 1H, J1=13.7 Hz, J2=2.6 Hz), 7.32 (t, 1H, J=9.0 Hz), 7.07 (m, 2H), 6.63 (d, 1H, J=5.5 Hz), 6.13 (d, 1H, J=7.6 Hz), 4.04 (s, br, 2H), 3.08 (s, 3H), 3.72 (m, 1H), 3.47 (t, 2H, J=5.2 Hz), 3.24 (s, 3H), 2.94 (m, 2H), 1.07 (s, 3H, 1.05 (s, 3H) (presumably a mono-TFA salt). MS: 513.4 (MH)+

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between EtOAc/NaHCO3 sat. solution
  3. filtrationThe solid was collected by filtration
  4. concentrationThe mixture was concentrated
  5. customthe residue was purified via Biotage (EA/MeOH 0-40%, 12 g Silicycle HR column)

Sources & evidence

ORD record
ord-c0690f1b758642808a61c893627c50f6
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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