Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1](Cl)(=[O:4])(=[O:3])[NH2:2].[C:6]1([CH2:12][CH2:13][CH2:14][OH:15])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C>C(#N)C>[S:1]([O:15][CH2:14][CH2:13][CH2:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:4])(=[O:3])[NH2:2]
Reactant: NS(=O)(=O)Cl
Reactant: OCCCc1ccccc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: NS(=O)(=O)OCCCc1ccccc1
Yield: 48 %

Procedure:
The title compound was obtained using the following procedure: The sulfamoyl chloride in solution prepared in (a) was reacted as in Example 12 with 16.4 g (0.118 mole) of 3-phenyl-1-propanol (98%) using 46.4 g (0.459 mole) of triethylamine in 100 ml of additional acetonitrile followed by using the extracting, washing and concentration procedures of Example 12 through the first evaporation. The viscous, oily residue was partitioned between water and ethyl ether (300 ml each). The organic layer was separated and washed with four 200 ml portions of water, the aqueous wash being finally neutral to pH paper. The organic layer was dried over magnesium sulfate and the solvent was evaporated under reduced pressure to give 19.5 g of a light-yellow, viscous oil which solidified on standing. The solid was recrystallized using ethyl ether and petroleum ether (bp range 30°-60° C.) to give 12.1 g (48%) of title compound as white solid, mp 56.5°-58° C.
Reaction SMILES: F[C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([F:11])[C:5]([C:12]([OH:14])=[O:13])=[C:4]([F:15])[C:3]=1[F:16].[CH3:17][Mg]Cl>C1COCC1>[F:11][C:6]1[C:5]([C:12]([OH:14])=[O:13])=[C:4]([F:15])[C:3]([F:16])=[C:2]([CH3:17])[C:7]=1[C:8]([OH:10])=[O:9]
Reactant: O=C(O)c1c(F)c(F)c(F)c(C(=O)O)c1F
Reactant: C[Mg]Cl
Solvent: C1CCOC1
Product: Cc1c(F)c(F)c(C(=O)O)c(F)c1C(=O)O

Procedure:
20 g of tetrafluoroisophthalic acid are initially charged in 250 ml of THF and, at from 20 to 40° C., admixed with 88 ml of a 3 molar methylmagnesium chloride solution. Customary aqueous work-up (see Example 3) gives 20.1 g of 2,4,5-trifluoro-6-methylisophthalic acid. The purity of the product is 85% by HPLC.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:24]([OH:26])=O)=[C:4]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH:7]=1.C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[N:40]1([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:44][CH2:43][CH2:42][CH2:41]1>CN(C=O)C>[CH3:1][C:2]1[C:3]([C:24]([N:48]2[CH2:49][CH2:50][CH:45]([N:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:46][CH2:47]2)=[O:26])=[C:4]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=2)[CH:7]=1
Reactant: C1CCN(C2CCNCC2)C1
Reactant: Cc1cc(-c2cccc(C(F)(F)F)c2)cc(-c2cncnc2)c1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1cc(-c2cccc(C(F)(F)F)c2)cc(-c2cncnc2)c1C(=O)N1CCC(N2CCCC2)CC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 99.1 %

Procedure:
0.05 g (0.1 mmol) of 5-methyl-3-pyrimidin-5-yl-3′-trifluoromethyl-biphenyl-4-carboxylic acid (intermediate 11) in 1.0 ml of oxalyl chloride (11.7 mmol) was treated at RT while stirring with one drop of DMF; after 30 min, the excess of oxalyl chloride was removed by evaporation in a high vacuum at RT. The residue was dissolved in 2.0 ml of CH2Cl2 and cooled down to 0° C.; then, 0.08 ml=0.056 g (0.6 mmol) of Et3N was added while stirring, followed by 0.022 g (0.1 mmol) of 4-pyrrolidin-1-yl-piperidine. The reaction mixture was subsequently warmed up to RT. After two hours, it was poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1) to give 0.049 g (71%) of the title compound as yellow solid. MS: 495.3 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:14](=[O:16])[CH3:15])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[Cl:17][C:18]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:19]=1[C:20](O)=[O:21]>>[Cl:17][C:18]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:19]=1[C:20]([N:11]1[CH2:12][CH2:13][N:8]([C:7]2[CH:6]=[CH:5][C:4]([C:14](=[O:16])[CH3:15])=[CH:3][C:2]=2[F:1])[CH2:9][CH2:10]1)=[O:21]
Reactant: CC(=O)c1ccc(N2CCNCC2)c(F)c1
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1Cl
Product: CC(=O)c1ccc(N2CCN(C(=O)c3cc([N+](=O)[O-])ccc3Cl)CC2)c(F)c1

Procedure:
The title compound was prepared according to the procedure D described for example 2 from 1-(3-Fluoro-4-piperazin-1-yl-phenyl)-ethanone and 2-chloro-5-nitro-benzoic acid (CAS: 2516-96-3); MS (ISP): 406.2 MH+.
Reaction SMILES: [SH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.Br[CH2:11][Cl:12].C(N(CC)CC)C>>[Cl:12][CH2:11][S:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1
Reactant: OCc1ccc(S)cc1
Reactant: ClCBr
Solvent: CCN(CC)CC
Product: OCc1ccc(SCCl)cc1

Procedure:
4-Mercaptobenzyl alcohol (see J.Chem.Soc 1963 p 1947) (5.0 mmol) was dissolved in bromochloromethane (100 mmol) and triethylamine (5 mmol) added dropwise. The resultant mixture was stirred for 1 hour at room temperature, washed with water and the dried (MgSO4) organic solution evaporated to leave the product. Yield 0.94g (95%) 1H NMR (CDCl3, δ): 2.03 (OH), 4.65 (CH2O), 4.90 (CH2S), 7.1-7.4 (Ph). The product needed no further purification for use in Example 33.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([CH2:10]O)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:32]>CN(C=O)C.C(Cl)Cl>[Br:32][CH2:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([OH:1])[CH:9]=1
Reactant: BrC(Br)(Br)Br
Reactant: N#Cc1ccc(CO)cc1O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: N#Cc1ccc(CBr)cc1O

Procedure:
2-Hydroxy-4-hydroxymethylbenzonitrile (0.20 g, 1.34 mmol) was dissolved in DMF (5 mL)—CH2Cl2(5 mL) and treated with triphenylphosphine (0.53 g, 2.01 mmol) and carbon tetrabromide (0.67 g, 2.01 mmol) at ambient temperature with stirring. After 2 h the reaction mixture was partitioned between EtOAc (100 mL)—H2O (100 mL), the organic layer separated, dried (MgSO4), and filtered to give the title compound after silica gel chromatography (15% EtOAc/hexane to 25% EtOAc/hexane).
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][C:5]([OH:7])=O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:27]([C:31]1[N:36]=[CH:35][C:34]([C:37]2[N:38]([C:58]([N:60]3[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]3)=[O:59])[C@@:39]([C:51]3[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=3)([CH3:50])[C@@:40]([C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=3)([CH3:42])[N:41]=2)=[C:33]([O:66][CH2:67][CH3:68])[CH:32]=1)([CH3:30])([CH3:29])[CH3:28]>CN(C)C=O>[C:27]([C:31]1[N:36]=[CH:35][C:34]([C:37]2[N:38]([C:58]([N:60]3[CH2:65][CH2:64][N:63]([C:5](=[O:7])[CH2:4][CH2:3][S:2][CH3:1])[CH2:62][CH2:61]3)=[O:59])[C@@:39]([C:51]3[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=3)([CH3:50])[C@@:40]([C:43]3[CH:44]=[CH:45][C:46]([Cl:49])=[CH:47][CH:48]=3)([CH3:42])[N:41]=2)=[C:33]([O:66][CH2:67][CH3:68])[CH:32]=1)([CH3:28])([CH3:29])[CH3:30]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCNCC1
Reactant: CSCCC(=O)O
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(C(=O)CCSC)CC1
Reaction time: 1 h
Yield: 89.4 %

Procedure:
To a solution of 3-(methylthio)propionic acid (30.8 mg, 0.256 mmole, Lancaster) in dimethylformamide (10 mL) were added successively 1-hydroxybenzotriazole (46.3 mg, 0.342 mmole, Chem-Impex), N,N,N′,N′-tetramethyl-O-(1H-Benzotriazol-1-yl)uranium hexafluorophosphate (130.0 mg, 0.343 mmole, Aldrich) and diisopropylethylamine (111.0 mg, 0.857 mmole). The mixture was stirred for 15 min before [(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (104.4 mg, 0.171 mmole) was added. The reaction mixture was allowed to stir for 1 h before concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with 1 N sodium hydroxide, brine, dried and concentrated. The crude residue was purified by flash column chromatography (silica gel, eluting with a gradient of 1-10% methanol in methylene chloride) to give the title compound (108.7 mg, 89% yield). HR-MS (ES, m/z) calculated for C37H46Cl2N5O3S [(M+H)+] 710.2693, observed 710.2691.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]#[C:5][CH2:6][Cl:7].O.[OH-].[Na+].[C:11]([O:15][C:16](=O)[O:17]C(C)(C)C)([CH3:14])([CH3:13])[CH3:12]>O1CCOCC1>[C:11]([O:15][C:16]([NH:2][CH2:3][C:4]#[C:5][CH2:6][Cl:7])=[O:17])([CH3:14])([CH3:13])[CH3:12]
Reactant: NCC#CCCl
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)NCC#CCCl
Reaction time: 0.5 h
Yield: 43.9 %

Procedure:
Ex-8c) 14.1 g of 1-Amino-4-chloro-2-butyne hydrochloride was taken up in 70 mL of dioxane and :35 mL water. 4 g NaOH was added and the reaction mixture was stirred for 30 minutes followed by the addition of 21.8 g di-t-butylcarbonate at 20° C. The reaction mixture was stirred at 20° C. to 25° C. for 8 h and then the lower organic layer was separated. The upper aqueous layer was extracted with 100 mL of dichloromethane. Organic layers were combined and washed with 50% aqueous NaHCO3, dried over anhydrous MgSO4, treated with Darco, filtered over celite and concentrated to give a brown oil. This oil was chromatographed to give 9 g of 1-t-Butyloxycarbonylamino-4-chloro-2-butyne as a white solid.
Reaction SMILES: [N+:1]([C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14]N(C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].BrC1C=CC([N+]([O-])=[O:31])=NC=1.N1CCOCC1>>[N+:1]([C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][O:31][CH2:14][CH2:15]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])nc2)CC1
Solvent: C1COCCN1
Product: O=[N+]([O-])c1ccc(N2CCOCC2)cn1

Procedure:
Following the procedures as described for 188a and starting with 2 g of 5-bromo-2-nitropyridine and 968 mg morpholine, 255a was obtained as a yellow solid (1 g, 50%). MS: [M+H]+ 210. 1H NMR (500 MHz, CDCl3) δ 8.18 (d, J=9.0, 1H), 8.15 (d, J=3.0, 1H), 7.22 (dd, J=3.0, 1H), 3.90 (t, J=5.0, 4H), 3.42 (t, J=5.0, 4H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[C:14]([F:21])=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH:16]=O.[OH-].[Na+]>C(O)(C)C>[Cl:12][C:13]1[C:14]([F:21])=[C:15](/[CH:16]=[C:6](/[C:5]2[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]([F:11])[CH:4]=2)\[C:7]#[N:8])[CH:18]=[CH:19][CH:20]=1
Reactant: O=Cc1cccc(Cl)c1F
Reactant: N#CCc1ccc(Cl)c(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Product: N#C/C(=C\c1cccc(Cl)c1F)c1ccc(Cl)c(F)c1
Temperature: 25 °C

Procedure:
A mixture of 4-chloro-3-fluorobenzylcyanide (1.0 g, 5.92 mmol), 3-chloro-2-fluorobenzaldehyde (0.938 g, 5.92 mmol), 2 N NaOH (4 mL) and isopropyl alcohol were stirred at rt. The mixture was stirred for 10 min. to afford a solid ppt that was collected by filtration with multiple water washes. The solid was dried ON under reduced pressure to afford a white solid (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-3-fluoro-phenyl)-acrylonitrile, 1.62 g, 89.3%;
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[NH:15][C:14]4[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:13]=4[N:12]=3)=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:24][Si:25]([CH2:28][CH2:29][O:30][CH2:31]Cl)([CH3:27])[CH3:26]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:15]([CH2:31][O:30][CH2:29][CH2:28][Si:25]([CH3:27])([CH3:26])[CH3:24])[C:14]4[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:13]=4[N:12]=3)=[N:9][N:8]([CH2:31][O:30][CH2:29][CH2:28][Si:25]([CH3:27])([CH3:26])[CH3:24])[C:5]2=[N:6][CH:7]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: COc1ccc2nc(-c3n[nH]c4ncc(Br)cc34)[nH]c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc2nc(-c3nn(COCC[Si](C)(C)C)c4ncc(Br)cc34)n(COCC[Si](C)(C)C)c2c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
5-bromo-3-(6-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridine Compound 19c (HOAc salt, 50 mg, 0.145 mmol) was added to a suspension of NaH (60% in mineral oil, 23 mg, 0.581 mmol) in DMF (5 mL). The mixture was stirred at r.t. for 5 mins, then SEMCl (97 mg, 0.581 mmol) was added. The mixture was stirred at r.t. for 12 hrs, then diluted with AcOEt (60 mL) and washed with water. The solvent was evaporated to dryness and the residue was purified by chromatography to provide 5-bromo-3-[6-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine Compound 20a (60 mg, 78% yield) as a sticky oil.
Reaction SMILES: C[Si]([N:5]=[N+:6]=[N-:7])(C)C.[C:8]([C:10]1[N:15]=[C:14]([O:16][CH3:17])[C:13]([N+:18]([O-:20])=[O:19])=[CH:12][CH:11]=1)#[CH:9]>C1(C)C=CC=CC=1.O>[CH3:17][O:16][C:14]1[C:13]([N+:18]([O-:20])=[O:19])=[CH:12][CH:11]=[C:10]([C:8]2[CH:9]=[N:7][NH:6][N:5]=2)[N:15]=1
Reactant: C#Cc1ccc([N+](=O)[O-])c(OC)n1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1nc(-c2cn[nH]n2)ccc1[N+](=O)[O-]
Temperature: 130 °C
Reaction time: 48 h
Yield: 231 %

Procedure:
Trimethylsilylazide (1.2 mL, 9.21 mmol) was added to a solution of 6-ethynyl-2-methoxy-3-nitropyridine (Preparation 200, 0.082 g, 0.460 mmol) in toluene (10.2 mL). The reaction mixture was stirred at 130° C. for 48 hours. The reaction was diluted with water and concentrated in vacuo. The residue was purified using Biotage silica gel column chromatography eluting with cyclohexane/EtOAc 70/30 to 50/50 to afford the title compound as a beige solid (235 mg, 77%).
Reaction SMILES: [CH2:1]([O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=2)[CH:17]=[C:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]2)=[N:11][CH:12]=1)[CH2:2][CH2:3][C:4]#[CH:5].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:33]=[CH:32][CH:31]=[C:16]([CH:17]=[C:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH:15]=2)=[N:11][CH:12]=1)[CH2:2][CH2:3][C:4]#[CH:5]
Reactant: C#CCCCOc1ccc(Oc2cccc(C=C3CCN(C(=O)OC(C)(C)C)CC3)c2)nc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C#CCCCOc1ccc(Oc2cccc(C=C3CCNCC3)c2)nc1
Reaction time: 0.5 h
Yield: 114.4 %

Procedure:
To a solution of tert-butyl 4-(3-(5-(pent-4-ynyloxy)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate (0.68 g, 1.33 mmol) in dry CH2Cl2 (3 mL) cooled to 0° C. was added TFA (1 mL, 13.3 mmol) dropwise. The mixture was stirred for 30 min. The reaction was concentrated and then partitioned between saturated NaHCO3 solution and CH2Cl2. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the title compound (0.53 g, 99%). m/z (421.2, MH+).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([O:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][NH2:19])[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](Cl)=[O:26]>>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([O:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][NH:19][C:25](=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][Cl:20])[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Cl)CCCCCl
Reactant: NC/C=C\COc1cc(CN2CCCCC2)ccn1
Product: O=C(CCCCCl)NC/C=C\COc1cc(CN2CCCCC2)ccn1
Yield: 93 %

Procedure:
Following a procedure similar to that described in Example 67(a), but using 4-(4-piperidinomethyl-2-pyridyloxy)-cis-2-butenylamine and 5-chlorovaleryl chloride as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained as an oil in a 93% yield.
Reaction SMILES: [CH3:1][P:2]([C:7]1[CH:12]=[C:11](Cl)[CH:10]=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])(=[O:6])[O:3][CH2:4][CH3:5].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[OH:23]>>[CH3:1][P:2]([C:7]1[CH:12]=[C:11]([O:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][N:17]=2)[CH:10]=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])(=[O:6])[O:3][CH2:4][CH3:5]
Reactant: CCOP(C)(=O)c1cc(Cl)ccc1[N+](=O)[O-]
Reactant: Oc1ccccn1
Product: CCOP(C)(=O)c1cc(Oc2ccccn2)ccc1[N+](=O)[O-]

Procedure:
Following the procedure of Example 17, ethyl P-methyl-2-nitro-5-chlorophenylphosphinate and 2-pyridyl alcohol are reacted together to give ethyl P-methyl-2-nitro-5-(2-pyridyloxy)phenylphosphinate.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[CH:8][C:9]([OH:11])=O)[CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:18]1([N:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25](=[O:32])[NH:26][CH2:27][CH2:28][CH2:29][CH2:30][NH2:31])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:18]1([N:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25](=[O:32])[NH:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:9](=[O:11])[CH:8]=[CH:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: NCCCCNC(=O)N(c1ccccc1)c1ccccc1
Reactant: O=C(O)C=Cc1cccnc1
Agent: O=C(Cl)C(=O)Cl
Product: O=C(C=Cc1cccnc1)NCCCCNC(=O)N(c1ccccc1)c1ccccc1

Procedure:
Batch size: 3.5 g (23.5 mmol) 3-(3-pyridyl)-acrylic acid, 4.0 g (31.5 mmol) oxalyl chloride and 6.0 g (21.1 mmol) 4-(3,3-diphenyl-ureido)-butylamine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH2:13])[CH2:7]1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1[CH2:26][C:27](O)=[O:28]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:27](=[O:28])[CH2:26][C:20]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:19]=2[Cl:18])[CH2:7]1
Reactant: O=C(O)Cc1cc(Cl)ccc1Cl
Reactant: NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Product: O=C(Cc1cc(Cl)ccc1Cl)NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Yield: 27.1 %

Procedure:
Example 13 was prepared in an analogous manner to Example 4 using a mixture of Intermediate 1 (0.055 g) and (2,5-dichlorophenyl)acetic acid (0.041 g) to give the title compound (0.025 g).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].[B:17](OCCCC)([O:23][CH2:24][CH2:25][CH2:26][CH3:27])[O:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[B:17]([O:16][C:6]1[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:10][C:9]([CH3:11])=[CH:8][C:7]=1[C:12]([CH3:15])([CH3:14])[CH3:13])([O:23][CH2:24][CH2:25][CH2:26][CH3:27])[O:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reactant: CCCCOB(OCCCC)OCCCC
Product: CCCCOB(OCCCC)Oc1c(C(C)(C)C)cc(C)cc1C(C)(C)C

Procedure:
Di-n-butyl 2,6-di-t-butyl-4-methylphenyl borate was prepared by reacting boric acid with n-butanol to give tri-n-butyl borate which was isolated by distillation. 2,6-di-t-butyl-4-methylphenol (1 mole) was added to the tri-n-butyl borate (1 mole). The reaction mixture was heated and n-butanol collected as distillate. The di-n-butyl 2,6-di-t-butyl-4-methylphenyl borate was isolated by distillation and its purity was confirmed by infra-red spectrascopy and chemical analysis.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH:9]=[CH2:10].C(=O)([O-])[O-].[K+].[K+].[CH2:17](Br)[CH:18]=[CH2:19].O>CC(C)=O>[CH:17]([O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH:9]=[CH2:10])=[CH:18][CH3:19]
Reactant: C=CCBr
Reactant: C=CCc1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: C=CCc1ccccc1OC=CC
Yield: 98.7 %

Procedure:
200 g of 3-(2-hydroxyphenyl)propene, 226 g of potassium carbonate and 180 g of allyl bromide were stirred in 490 ml of acetone at reflux temperature for 23 hours and then cooled. One liter of water was added and the resultant layers were separated. The aqueous layer extracted with two volumes of diethyl ether, dried and stripped of solvent to give 256 g of 3-(2-propenyloxyphenyl)propene which was subsequently rearranged as described in Example 56 to the 2,6-di-propenylphenol intermediate. 52.2 g of said intermediate was dissolved in 500 ml of THF and chilled to -5° C. 300 ml of one molar borane was added over 15 minutes (maximum temperature not exceeding 18° C.), after which the mixture was stirred for 36 hours and chilled to 0° C. 80 ml of water was added over a 5 minute period, after which 120 ml of 5N sodium hydroxide was added all at once. When the temperature of the reaction mixture reached 1° C., 81 ml of 30% hydrogen peroxide was added over a 25 minute period and the mixture stirred for one hour and then concentrated. An additional 500 ml of water and 250 ml of ethyl acetate were added which, following workup, gave about 54 g of the desired 2,6-di(3-hydroxypropyl)phenol intermediate, m.p. 176°-187° C.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=2[O:14][CH:15]([F:17])[F:16])[CH:9]=[O:10])[CH2:3][CH2:2]1.[CH3:18][Mg+].[Br-].[NH4+].[Cl-]>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:9]([OH:10])[CH3:18])[CH:11]=[CH:12][C:13]=2[O:14][CH:15]([F:16])[F:17])[CH2:3][CH2:2]1
Reactant: C[Mg+]
Reactant: O=Cc1ccc(OC(F)F)c(OCC2CC2)c1
Agent: [Br-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(O)c1ccc(OC(F)F)c(OCC2CC2)c1
Yield: 93.9 %

Procedure:
In THF, dissolved was 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde (24 g, 99 mmol), and 3M CH3MgBr (49 ml, 148 mmol) was added thereto at −78° C. The reaction mixture was neutralized with NH4Cl, and extracted with EA. The extract was washed twice with brine, dried over MgSO4, filtered and evaporated under reduced pressure to remove solvent. The mixture was purified via column chromatography (n-hexane/EA=1/1) to obtain 1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]ethanol (24 g, 94%).
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[F:14][C:15]([F:27])([F:26])[C:16]1[CH:25]=[CH:24][C:19]([C:20](=O)[CH2:21]Br)=[CH:18][CH:17]=1>>[F:14][C:15]([F:26])([F:27])[C:16]1[CH:17]=[CH:18][C:19]([C:20]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[O:3][CH:21]=2)=[CH:24][CH:25]=1
Reactant: O=C(CBr)c1ccc(C(F)(F)F)cc1
Reactant: COC(=O)c1ccc(C(N)=O)cc1
Product: COC(=O)c1ccc(-c2nc(-c3ccc(C(F)(F)F)cc3)co2)cc1
Yield: 30 %

Procedure:
In the same manner as in Example 1, methyl 4-carbamoylbenzoate was reacted with 4-trifluoromethylphenacyl bromide to obtain methyl 4-[4-(4-trifluoromethylphenyl)-2-oxazolyl]benzoate. The product was recrystallized from ethanol. Yield: 30%. Pale yellow prisms. Melting Point: 182 to 183° C.
Reaction SMILES: [O-:1][CH2:2][CH3:3].[Na+].[Na].CCO.[CH3:9][O:10][C:11]1[CH:38]=[CH:37][C:14]([CH2:15][N:16]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[C:28](Cl)[N:27]=2)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1>C1COCC1>[CH3:9][O:10][C:11]1[CH:38]=[CH:37][C:14]([CH2:15][N:16]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[C:28]([O:1][CH2:2][CH3:3])[N:27]=2)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2ccc(C(F)(F)F)c(Cl)n2)cc1
Reactant: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOc1nc(N(Cc2ccc(OC)cc2)Cc2ccc(OC)cc2)ccc1C(F)(F)F
Temperature: 25 °C

Procedure:
Add freshly prepared sodium ethoxide [made by adding sodium (1.26 g, 54.9 mmol) to 25 mL of absolute EtOH, and stirring until all the sodium is dissolved] dropwise to a solution of N,N-bis-(4-methoxybenzyl)-(6-chloro-5-trifluoromethyl-pyridine-2-yl)amine (8.0 g, 18.3 mmol) in 150 mL THF. Heat the reaction mixture to reflux for 45 hours. During reflux, the reaction mixture turns brown. After cooling to room temperature, remove the solvent under vacuum. Take up the residue in CH2Cl2 (150 mL) and wash with water (100 mL). Extract the aqueous layer once more with 100 mL CH2Cl2. Wash the combined CH2Cl2 extracts with brine (100 mL), dry (Na2SO4), filter, and evaporate to give a brown oil/solid mix. Purification by column chromatography affords the title product as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.51 (d, 1H, J=8.8 Hz), 7.13 (m, 4H), 6.86 (m, 4H), 6.0 (d, 1H, J=8.8 Hz), 4.67 (s, 4H), 4.37 (q, 2H, J=6.8 and 7.6 Hz), 3.80 (s, 6H), 1.32 (t, 3H, J=6.8 Hz). Mass spec. (447.34, M+H).