Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O=[C:16]1[CH2:24][CH2:23][C:22]2[C:18](=[CH:19][N:20]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[N:21]=2)[CH2:17]1.[CH:35]1([NH2:38])[CH2:37][CH2:36]1.C(=O)(O)[O-].[Cl:43]CCCl>O.C(O)(=O)C>[ClH:43].[CH:35]1([NH:38][CH:16]2[CH2:24][CH2:23][C:22]3[C:18](=[CH:19][N:20]([C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[N:21]=3)[CH2:17]2)[CH2:37][CH2:36]1
Reactant: O=C1CCc2nn(C(=O)OCc3ccccc3)cc2C1
Reactant: ClCCCl
Reactant: NC1CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Cl
Product: O=C(OCc1ccccc1)n1cc2c(n1)CCC(NC1CC1)C2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Sodium triacetoxy borohydride (5.41 g) and acetic acid (2.19 mL) were added to a mixture of a mixture (3.45 g) of benzyl 5-oxo-4,5,6,7-tetrahydro-2H-indazole-2-carboxylate and a regioisomer thereof, cyclopropylamine (0.878 mL), and 1,2-dichloroethane (70 mL) under an argon gas atmosphere, followed by stirring for 18 hours at room temperature. Water was added to the reaction liquid, followed by stirring for 2 hours at room temperature, and then pH thereof was adjusted to 8 by using saturated aqueous bicarbonate, followed by liquid separation. The organic layer was dried and then concentrated under reduced pressure. A dioxane solution (4.15 mL) of 4 M hydrogen chloride was added to a mixture of the residue and ethyl acetate (100 mL), followed by stirring for an hour at room temperature. The precipitate was collected by filtration and washed with ethyl acetate, thereby obtaining a mixture (3.26 g) of benzyl 5-(cyclopropylamino)-4,5,6,7-tetrahydro-2H-indazole-2-carboxylate monohydrochloride and a regioisomer thereof.
Reaction SMILES: [CH:1]1([N:7]2[CH2:13][C:12]([F:16])([CH:14]=[CH2:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)C[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:59][CH:60]1[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]1>>[CH:1]1([N:7]2[CH2:13][C:12]([F:16])([CH:14]=[CH2:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([NH:59][CH:60]5[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]5)=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CN1CCC(N)CC1
Reactant: C=CC1(F)CN(C2CCCCC2)c2nc(Nc3ccc(C(=O)O)cc3OC)ncc2N(C)C1=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: C=CC1(F)CN(C2CCCC2)c2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)ncc2N(C)C1=O

Procedure:
The title compound was synthesized from 4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 4-amino 1-N-methyl piperidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53-1.86 (m, 8 H) 1.93 (t, J=10.86 Hz, 4 H) 2.16 (s, 3 H) 2.78 (d, J=11.12 Hz, 2 H) 3.28 (s, 3 H) 3.65-3.83 (m, 4 H) 3.93 (s, 3 H) 4.88 (m, 1 H) 5.38 (d, J=11.87 Hz, 2 H) 6.01 (m, 1 H) 7.48 (d, J=8.0 Hz, 1 H), 7.49 (br. s., 1 H) 7.82 (s, 1 H) 8.12 (s, 1 H) 8.12 (d, J=7.83 Hz, 1 H) 8.30 (d, J=8.0 Hz, 1 H). [M+H] calculated for C29H38FN7O3, 552; found 552.
Reaction SMILES: C([O-])(=O)C.[Na+].[NH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:20]([O:22][CH3:23])=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1.Cl[C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[N:26]=1>O1CCCC1>[CH3:23][O:22][C:20]([C:15]1[C:14]([C:11]2[CH:12]=[CH:13][C:8]([CH2:7][NH:6][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]=[C:27]([C:35]([F:37])([F:38])[F:36])[N:26]=3)=[CH:9][CH:10]=2)=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:21]
Reactant: FC(F)(F)c1nc(Cl)c2ccccc2n1
Reactant: COC(=O)c1ccccc1-c1ccc(CN)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccccc1-c1ccc(CNc2nc(C(F)(F)F)nc3ccccc23)cc1
Reaction time: 72 h
Yield: 110.8 %

Procedure:
Sodium acetate (2.34 g), 4'-aminomethyl(1,1'-biphenyl)-2-carboxylic acid, methyl ester (1.99 g) and 1.66 g of 4-chloro-2-trifluoromethylquinazoline were added to 50 mL of tetrahydrofuran. The resulting suspension was stirred at 40°-50° C. for 72 hours. All the THF was removed by evaporation and the residue was partitioned between ethyl acetate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel chromatography to yield. 3.46 g (40%) of the desired product (M.P.=135°-142° C.): 1H NMR (DMSO-d6, 400 MHz) δ 9.43 (t, J=6 Hz, 1H), 8.41 (d, 7.9 Hz, 1H), 7.88 (m, 2H), 7.70 (m, 2H), 7.58 (m, 1H), 7.43 (m, 4H), 7.25 (m, 2H), 4.85 (d, J=5.9 Hz, 2 H), 3.56 (s, 3H); positive FAB MS m/e 438 (MH). Anal Calcd for C24H18F3N3O2.0.5H2O: C, 64.57; H, 4.29; N, 9.41. Found: C, 64.83; H, 4.02; N, 9.48.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][N:23]=1)([CH3:16])([CH3:15])[CH3:14].[I:24]I.S([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[C:13]([O:17][C:18]1[C:19]([I:24])=[N:20][CH:21]=[CH:22][N:23]=1)([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(C)(C)Oc1cnccn1
Reactant: II
Agent: O=S([O-])[O-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)Oc1nccnc1I
Reaction time: 0.5 h
Yield: 6.2 %

Procedure:
To a solution of 5.64 g of diisopropylamine in 100 ml of THF there was added 21.1 ml of n-butyllithium (2.55M, n-hexane solution) at −75° C. under a nitrogen atmosphere, and after stirring the mixture for 30 minutes, a solution of 6.78 g of 3-t-butoxypyrazine [CAS No. 70090-30-1] in 30 ml of THF was added dropwise. After stirring at the same temperature for 4 hours, a solution of 17.9 g of iodine in 100 ml of THF was added dropwise and the mixture was stirred overnight at room temperature. Next, 800 ml of saturated aqueous sodium sulfite and 800 ml of ethyl acetate were added, and the organic layer was washed with 300 ml of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate) to give 2-t-butoxy-3-iodopyrazine (0.77 g) as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH2:19])=[N:10][NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[CH3:20][N:21]=[C:22]=[O:23]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([NH:19][C:22]([NH:21][CH3:20])=[O:23])=[N:10][NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:6][CH:7]=1
Reactant: CN=C=O
Reactant: Nc1n[nH]c(-c2ccncc2)c1-c1ccc(F)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CNC(=O)Nc1n[nH]c(-c2ccncc2)c1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-pyrazol-3-amine prepared as set forth in Example 2 (100 mg, 0.38 mmol), methyl isocyanate (22 mg, 0.39 mmol) and 4-dimethylaminopyridine (2.5 mg) in methylene chloride (10 ml) was stirred at room temperature for 30 minutes. The reaction was stripped in vacuo. The residue was triturated with hexane and the solid filtered to give pure N-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-pyrazol-3-yl]-N′-methylurea, m.p. 212–213° C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[C:21]#[N:22].Cl.N1C=CC=CC=1.[N-:36]=[N+:37]=[N-:38].[Na+].O>CN(C=O)C>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:19]=[C:20]([C:21]2[NH:38][N:37]=[N:36][N:22]=2)[CH:23]=[CH:24][CH:25]=1
Reactant: N#Cc1cccc(OCc2cccc(OCc3ccc4ccccc4n3)c2)c1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Solvent: O
Product: c1cc(COc2cccc(-c3nnn[nH]3)c2)cc(OCc2ccc3ccccc3n2)c1
Temperature: 100 °C

Procedure:
A mixture of 1.2 g (3.28 mmol) of 3-[3-(2-quinolinylmethyloxy)benzyloxy]benzonitrile, 1.89 g (16.4 mmol) of pyridine hydrochloride, and 1.06 g (16.4 mmol) of sodium azide in 10 ml of DMF is heated at 100° C. for 4 days. The reaction mixture is poured into water. The crude product collected on a filter and recrystallized from ethyl acetate to give 5-[3-(3-(2-quinolinylmethyloxy)benzyloxy)phenyl] tetrazole. (M.P. 169°-172° C.)
Reaction SMILES: [CH2:1]([O:5][Zr:6](OCCCC)(OCCCC)[O:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2][CH2:3][CH3:4].C(CC(=O)C)(=O)C>C1(C)C=CC=CC=1>[CH2:8]([O:7][Zr:6][O:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH2:9][CH2:10][CH3:11]
Reactant: CCCCO[Zr](OCCCC)(OCCCC)OCCCC
Solvent: CC(=O)CC(C)=O
Solvent: Cc1ccccc1
Product: CCCCO[Zr]OCCCC

Procedure:
In 87 g of toluene was dissolved 38.3 g (0.1M) of tetra-n-butoxyzirconium, and 20.0 g (0.2M) of acetylacetone was gradually added to the resulting solution with stirring. An exothermic reaction of the mixture took place to give di-n-butoxyzirconium bisacetylacetonato.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]([CH2:6][CH2:7][NH:8][C:9](=[O:27])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][CH2:17][CH2:18][CH2:19]N2CCSCC2)=[C:12]([NH2:26])[CH:11]=1)=[O:5].C(O[CH2:32][CH3:33])(=O)C.[CH2:34](O)[CH3:35]>>[CH3:2][O:3][C:4]([CH2:6][CH2:7][NH:8][C:9](=[O:27])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][CH2:17][CH2:18][CH2:19][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:34][CH2:35][CH2:32][CH3:33])=[C:12]([NH2:26])[CH:11]=1)=[O:5]
Reactant: CCOC(C)=O
Reactant: CCO
Reactant: COC(=O)CCNC(=O)c1ccc(NCCCN2CCSCC2)c(N)c1
Agent: Cl
Product: CCCCCCCCCCCCCCNc1ccc(C(=O)NCCC(=O)OC)cc1N

Procedure:
The same procedure is used as in (2). Rf value: 0.55 (silica gel; ethyl acetate/ethanol=50:2)
Reaction SMILES: [Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](OCC)=O)[N:27]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+:34].C[Al](C)C.C(O)(=O)C.C(OCC)(=O)C>C1C=CC=CC=1>[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]#[N:34])[N:27]=2)[CH2:20]1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1csc(N2CC(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)C2)n1
Reactant: [NH4+]
Agent: C[Al](C)C
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CC(C)(C)[Si](OC1CN(c2nc(C#N)cs2)C1)(c1ccccc1)c1ccccc1
Temperature: 50 °C
Reaction time: 17 h
Yield: 76 %

Procedure:
To a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (7.73 g, 16.6 mmol) (obtained as described in Reference Example 2(1)) in benzene (370 ml) was added a solution of 0.67M ammonium chloride-trimethylaluminium in benzene (75 ml) at room temperature under an atmosphere of nitrogen. The mixture was stirred in a water bath (50° C.) for 17 hours. After checking the completion of the reaction, 10% aqueous acetic acid solution (100 ml) and ethyl acetate (50 ml) were added to the reaction mixture in an ice bath and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (3:1) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-cyano-1,3-thiazol-2-yl)azetidine (6.98 g, yield 76%) as a pale brown solid.
Reaction SMILES: CN([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[NH:12][C:13]3[CH:14]=[C:15]([NH:25]C(=O)C4C=CC=C(C(F)(F)F)C=4F)[CH:16]=[C:17]4[C:23](=[O:24])NN=C[C:19]=2[C:18]=34)[CH:8]=[CH:9][CH:10]=1)C.Cl.[O:40]1CCOC[CH2:41]1.C[OH:47]>>[CH3:41][O:40][C:23]([C:17]1[C:18]2[CH:19]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([CH2:4][OH:47])[CH:6]=3)[NH:12][C:13]=2[CH:14]=[C:15]([NH2:25])[CH:16]=1)=[O:24]
Reactant: CO
Reactant: CN(C)Cc1cccc(-c2[nH]c3cc(NC(=O)c4cccc(C(F)(F)F)c4F)cc4c3c2C=NNC4=O)c1
Reactant: C1COCCO1
Agent: Cl
Product: COC(=O)c1cc(N)cc2[nH]c(-c3cccc(CO)c3)cc12
Temperature: 90 °C

Procedure:
Intermediate 73(c) from Example 73 (1.8 g, 5 mmol) was dissolved in methanol (22 mL). 4M HCl in dioxane (22 mL, 75 mmol) was carefully added, and the solution was heated at 90° C. for 1 hour. After cooling to 22° C., the volatiles were removed in vacuo giving 6-amino-2-(3-hydroxymethyl-phenyl)-1H-indole-4-carboxylic acid methyl ester which was then combined with (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (2 g, 12.5 mmol), triethylamine (3.5 mL, 25 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (4.7 g, 12.5 mmol) in N,N-dimethylformamide (0.2 M, 25 mL) and stirred at 22° C. for 12 hours. Volatiles were removed in vacuo and the crude mixture dissolved in methanol (25 mL, 0.2 M) was treated with K2CO3 (1.38 g, 10 mmol) for 1 hour at 22° C. Excess K2CO3 was removed by filtration, and acetic acid (2 drops) was added to the filtrate. Following filtrate evaporation, the residue was subjected to silica gel chromatography (90:10 to 100:0 ethyl acetate/hexane) which provided Intermediate 85(a) (1.1 g, 2.5 mmol) in 50% yield.
Reaction SMILES: N1C=CC=CC=1.[Br:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11]O.P(Br)(Br)[Br:18].P([O-])([O-])[O-]>C1(C)C=CC=CC=1>[Br:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11][Br:18]
Reactant: OCc1ccc(F)c(Br)c1
Reactant: BrP(Br)Br
Agent: [O-]P([O-])[O-]
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: Fc1ccc(CBr)cc1Br
Temperature: -10 °C
Reaction time: 1 h

Procedure:
Pyridine (0.7 cm3) and a solution of 3-bromo-4-fluorobenzyl alcohol (5 g) in dry toluene (50 cm3) were added to a stirred solution of phosphorus tribromide (2.64 g) in dry toluene (50 cm3) under an atmosphere of nitrogen, the temperature of the reaction mixture being maintained at -10° C. during the addition. The mixture was allowed to warm to the ambient temperature (ca. 20° C.) and was stirred for one hour. The mixture was poured into ice and the products extracted into diethyl ether. The combined organic extracts were washed with brine and dried over anhydrous magnesium sulphate to give an orange-red oil, shown by thin layer chromatography to contain two components. NMR spectroscopy of the mixture suggested the presence of a phosphite intermediate and the required product. The oil was redissolved in dry toluene (50 cm3) and further phosphorus tribromide (0.2 g) and pyridine (0.7 cm3) added. The mixture was stirred at 50° C. for 4 hours and then stood at the ambient temperature for 17 hours. The mixture was poured into ice and sodium bicarbonate solution added to neutralise the resulting acid mixture. The products were extracted into diethyl ether, and the combined organic extracts washed with brine and dried over anhydrous magnesium sulphate. Evaporation of the solvent gave a white solid which was purified by flash column chromatography on a silica gel support, eluting with petroleum ether containing 5% by volume diethyl ether, to give the title compound (4.6 g) as a colourless crystalline solid.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:20](O)=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1.C(OCC)(=O)C.O>O1CCCC1>[CH3:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][OH:21])=[CH:12][CH:13]=1
Reactant: Cc1ccc(-c2ccccc2C(=O)O)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(-c2ccccc2CO)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 84.6 %

Procedure:
To an ice-cooling suspension of lithium aluminium hydride (1.79 g) in tetrahydrofuran (50 ml) was added dropwise a solution of 4'-methylbiphenyl-2-carboxylic acid (5.0 g) in tetrahydrofuran (30 ml). The mixture was stirred for 17 hours at room temperature. To the reaction mixture were added ethyl acetate (10 ml) and water (50 ml), and insoluble materials were removed by filtration through celite. The filtrate was concentrated to dryness, and the residue was dissolved in ethyl acetate. The solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and dried. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel to afford the title compound as colorless syrup (3.95 g, 84%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[O:6][CH:7]=[CH:8][C:9]=1[NH:10]C(=O)OC(C)(C)C)=[O:4].FC(F)(F)C(O)=O>ClCCl>[NH2:10][C:9]1[CH:8]=[CH:7][O:6][C:5]=1[C:3]([O:2][CH3:1])=[O:4]
Reactant: COC(=O)c1occc1NC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1occc1N
Temperature: 25 °C
Reaction time: 3 h
Yield: 86.1 %

Procedure:
Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86%): MS (Q1) 142 (M)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:19]([F:22])([F:21])[F:20])=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([N+:13]([O-])=O)[CH:10]=[CH:9][C:8]=1[O:16][CH3:17].O.O.Cl[Sn]Cl>CCO>[Cl:1][C:2]1[C:3]([C:19]([F:22])([F:20])[F:21])=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][C:8]=1[O:16][CH3:17]
Reactant: COc1ccc([N+](=O)[O-])cc1-c1c(Cl)c(C(F)(F)F)nn1C
Agent: Cl[Sn]Cl
Solvent: CCO
Solvent: O
Product: COc1ccc(N)cc1-c1c(Cl)c(C(F)(F)F)nn1C
Yield: 66.7 %

Procedure:
To a stirred solution of 4-chloro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-3-trifluoromethyl-1H-pyrazole (0.11 g, 0.33 mmol) in EtOH (1.0 mL) was added SnCl2.2H2O (0.30 g, 1.31 mmol, 4.0 eq.) and the mixture was stirred at reflux for 2 hours followed by the removal of EtOH under vacuum. The resulting solid was dissolved in EtOAc and 1N NaOH was added until the pH was adjusted to 6. The mixture was stirred overnight and filtered through celite. The aqueous phase was extracted with EtOAc (3×50 mL). The combined organic phase was dried over anhydrous MgSO4, filtered and evaporated to give 3-(4-chloro-2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine (0.067 g, 0.22 mmol, 66% yield after two steps) as a white solid: LCMS m/z (%)=306 (M+H35Cl, 100), 308 (M+H37Cl, 33). 1H NMR (400 MHz, CDCl3) δ: 6.86 (dd, J=14.0, 6.0 Hz, 1H), 6.84 (dd, J=8.0, 4.0 Hz, 1H), 6.63 (d, J=4.0 Hz, 1H), 3.74 (s, 3H), 3.72 (s, 3H).
Reaction SMILES: [I-].[NH:2]1[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[CH2:7][CH2:6][C:5]=2[C:4]([CH2:15][N+:16]([CH3:19])([CH3:18])C)=[N:3]1.[C:20]1(/[CH:26]=[CH:27]/[C:28]2[CH2:29]CNC[CH:33]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.O>CN(C=O)C>[C:20]1(/[CH:26]=[CH:27]/[C:28]2[CH2:29][CH2:19][N:16]([CH2:15][C:4]3[C:5]4[CH2:6][CH2:7][C:8]5[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=5[C:10]=4[NH:2][N:3]=3)[CH2:18][CH:33]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: C[N+](C)(C)Cc1n[nH]c2c1CCc1ccccc1-2
Reactant: C1=C(/C=C/c2ccccc2)CCNC1
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C1=C(/C=C/c2ccccc2)CCN(Cc2n[nH]c3c2CCc2ccccc2-3)C1

Procedure:
A solution of (4,5-dihydro-1H-benzo[g]indazol-3-ylmethyl)-trimethylammonium iodide (0.20 g), 4-((E)-2-phenylethenyl)-1,2,3,6-tetrahydropyridine (0.085 g) and diisopropylethylamine (0.10 cm3) in DMF (10 cm3) was heated under nitrogen at 80° C. for 48 hours. The mixture was cooled, poured into water (50 cm3) and extracted with 10% ethyl acetate-diethyl ether (2×50 cm3). The extracts were dried (MgSO4), filtered and concentrated to give a brown oil. Preparative thin layer chromatography on silica gel, eluting with 5% methanol-dichloromethane+1% ammonia, gave the title compound as a brown foam, which was crystallised as the oxalate salt from ethanol to give beige granules (0.007 g; 3%), m.p. 205°-210° C. (from EtOH); δH (360 MHz; d6 -DMSO+CF3CO2H) 2.54-2.70 (2H, m, NCH2CH2), 2.76 (2H, t, J 7.5, --CH2 --), 2.92 (2H, t, J 7.5, --CH2 --), 3.12-3.32 (1H, m, NCHAHBCH2), 3.60-3.78 (1H, m, NCHAHBCH2), 3.82-4.00 (2H, m, NCH2CH=C), 4.40 (2H, broad s, --CH2N), 5.90 (1H, s, NCH2 CH=C), 6.60 (1H, d, J 16.3, CH=CHPh), 6.96 (1H, d, J 16.3, CH=CHPh) 7.22-7.35 (6H, m, 6 of ArH), 7.49 (2H, d, J 7.4, 2 of ArH) and 7.64 (1H, d, J 6.6, 1 of ArH); m/z (CI+ ; NH3) 368 (MH+ ; 10%), 298 (10), 188 (15), 186 (20) and 184 (100). Found: M+ 367.2039. C25H25N3 requires 367.2048.
Reaction SMILES: COC1C=C(C=CC=1OC)C(C1C=CC(OC)=C(OC)C=1)=O.[C:23]1([O:31][CH3:32])[C:24](=[CH:27][CH:28]=[CH:29][CH:30]=1)[O:25][CH3:26].[Cl-].[Al+3].[Cl-].[Cl-].[Cl:37][C:38]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:39]=1[C:40](Cl)=[O:41]>>[Cl:37][C:38]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:39]=1[C:40](=[O:41])[C:29]1[CH:28]=[CH:27][C:24]([O:25][CH3:26])=[C:23]([O:31][CH3:32])[CH:30]=1
Reactant: O=C(Cl)c1cc(Cl)ccc1Cl
Reactant: COc1ccccc1OC
Agent: COc1ccc(C(=O)c2ccc(OC)c(OC)c2)cc1OC
Agent: [Al+3]
Agent: [Cl-]
Product: COc1ccc(C(=O)c2cc(Cl)ccc2Cl)cc1OC

Procedure:
2′,5′-Dichloro-3,4-dimethoxybenzophenone was prepared analogously to 3,4,3′,4′-tetramethoxybenzophenone using veratrole (2.15 mL, 15 mmol), aluminum chloride (2.2 g, 16.5 mmol) and 2,5-dichlorobenzoyl chloride (1.9 mL, 15 mmol) with a reaction time of 3 hours at reflux. The crude product was purified by flash column chromatography (silica gel, 2.5% ethyl acetate/methylene chloride) to afford 3.88 g (83%) of the product as a white solid: mp 129-130° C.; 1H NMR (CDCl3) δ7.65-7.56 (m, 1 H), 7.41-7.12 (m, 4 H), 6.89-6.81 (m, 1 H), 3.96 (s, 3 H), 3.94 (s, 3 H); 13C NMR (CDCl3) δ191.1, 154.4, 149.6, 137.9, 132.0, 130.5, 128.7, 128.0, 125.7, 110.2, 56.1, 56.0; Anal. Calcd for C15H12Cl2O3. Theoretical: C, 57.90; H, 3.89. Found: C, 57.58; H, 3.87.