Trifluoroacetic acid → 1-(4-(2-(5-((Azetidin-3-yloxy)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea

HRID 1400932Notes

Reaction equation

HRID 1400932 reaction equation
[CH:1]1([NH:4][C:5](=[O:43])[NH:6][C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][O:28][CH:29]6[CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:31]1[CH2:30][CH:29]([O:28][CH2:27][C:24]2[CH:23]=[CH:22][C:21]([C:19]3[S:20][C:13]4[C:14](=[N:15][CH:16]=[CH:17][C:12]=4[O:11][C:10]4[CH:40]=[CH:41][C:7]([NH:6][C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)=[O:43])=[CH:8][C:9]=4[F:42])[CH:18]=3)=[N:26][CH:25]=2)[CH2:32]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67443636Tert-butyl 3-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methoxy)azetidine-1-carboxylate

Product 1

HCID 674417991-(4-(2-(5-((Azetidin-3-yloxy)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylureaYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 404 (221 mg, 0.365 mmol) in DCM (5 mL) was added TFA (1 mL) and the reaction mixture was stirred for 4 h then concentrated, diluted with water and 1M NaOH to pH 11. The solid was collected by filtration, rinsed with water and dried. The residue was purified by Biotage (SNAP 25 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 10/90 to 30/70), to afford the title compound 405 (155 mg, 84% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.77 (s, 1H), 8.55 (brd, J=1.6 Hz, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.35 (s, 1H), 8.27 (d, J=7.2 Hz, 1H), 7.91 (dd, J=8.0, 2.4 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.24-7.18 (m, 1H), 6.65 (d, J=5.2 Hz, 1H), 6.62 (brd, J=2.8 Hz, 1H), 4.48 (s, 2H), 4.40-4.41 (m, 1H), 3.56-3.49 (m, 2H), 3.47-3.50 (m, 2H), 2.58-2.51 (m, 1H), 0.68-0.62 (m, 2H), 0.47-0.41 (m, 2H). MS (m/z): 506.14 (M+H).

Workup

  1. concentrationthen concentrated
  2. additiondiluted with water and 1M NaOH to pH 11
  3. filtrationThe solid was collected by filtration
  4. washrinsed with water
  5. customdried
  6. customThe residue was purified by Biotage (SNAP 25 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 10/90 to 30/70)

Sources & evidence

ORD record
ord-6bc178e0ac0a459c8e85c53209121326
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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