Phenylacetyl isothiocyanate → 1-(4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(2-phenylacetyl)thiourea

HRID 2241182Notes

Reaction equation

HRID 2241182 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[CH:10]=[N:9]2)=[CH:5][CH:4]=1.[C:28]1([CH2:34][C:35]([N:37]=[C:38]=[S:39])=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:38]([NH:37][C:35](=[O:36])[CH2:34][C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)=[S:39])=[CH:20][C:19]=4[F:25])=[C:11]3[CH:10]=[N:9]2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 12454157Phenylacetyl isothiocyanateHCID 685158574-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

Product 1

HCID 866156021-(4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(2-phenylacetyl)thioureaYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.504 g, 1.38 mmol; obtained from Example 1, Step D in THF (5 mL) was added 2-phenylethanoyl isothiocyanate (0.294 g, 1.66 mmol; prepared according to J. Org. Chem. 1964, 29, 1115-1119). The reaction was stirred at room temperature for 30 minutes. The reaction mixture was loaded directly onto a preparative TLC plate, eluting with 5% MeOH/DCM. The product was obtained as a waxy solid (630 mg, 71%). LRMS (APCI+): 93% purity, 220 nm, m/z 542 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 12.49 (br s, 1H), 8.50 (br s, 1H), 8.38 (d, J=5.5 Hz, 1H), 7.94 (m, 1H), 7.82 (s, 1H), 7.42 (m, 4H), 7.32 (m, 4H), 7.26 (m, 1H, overlaps CHCl3), 6.83 (d, J=8.6 Hz, 2H), 6.42 (d, J=5.5 Hz, 1H), 5.63 (s, 2H), 3.76 (s, 3H), 3.75 (s, 2H); 19F NMR (376 MHz, CDCl3) δ −126.3 (m).

Workup

  1. washeluting with 5% MeOH/DCM

Sources & evidence

ORD record
ord-cf00bb9f8999483b9c87c877fdf28efe
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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