Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]1[O:12][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:13][CH:14]([NH2:17])[CH2:15][NH2:16]>>[CH2:15]([NH:16][CH2:1][CH:2]([OH:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH:14]([NH:17][CH2:1][CH:2]([OH:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH3:13]
Reactant: CCCCCCCCCC1CO1
Reactant: CC(N)CN
Product: CCCCCCCCCC(O)CNCC(C)NCC(O)CCCCCCCCC

Procedure:
Condensation of 1-undecene oxide and 1-methyl-1,2-ethanediamine affords N,N'-(1,2-propylene)-bis[2-hydroxyundecylamine] (I: R = CH3 (CH2)8, R' = H, X = CH(CH3)CH2, Z = H).
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5](O)=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2].C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:24])=O>O>[Cl:24][C:5]1[C:4]([O:3][CH2:1][CH3:2])=[CH:9][CH:8]=[CH:7][N:6]=1
Reactant: CCOc1cccnc1O
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)c1ccccc1
Solvent: O
Product: CCOc1cccnc1Cl
Temperature: 150 °C
Yield: 70.5 %

Procedure:
A mixture of 3-ethoxy-pyridin-2-ol (4.0 g, 28.8 mmol, 1.0 equiv), N,N-diethylaniline (4.61 mL, 4.29 g, 28.8 mmol, 1.0 equiv) and phosphorus oxychloride (2.62 mL, 4.41 g, 28.8 mmol, 1.0 equiv) was heated to 150° C. under microwave irradiation for 20 min. The crude reaction mixture was poured into water (100 mL), the solution adjusted to pH 7 and extracted with dichloromethane (3×100 mL). The combined organic phases were dried over MgSO4, the solvent removed by evaporation under reduced pressure and the crude material purified with column chromatography on silica eluting with hexane/ethyl acetate (4:1) providing 3.2 g (71%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.50 (t, J=7.0 Hz, 3H), 4.12 (q, J=7.0 Hz, 2H), 7.18 (d, J=3.2 Hz, 2H), 7.98 (t, J=3.2 Hz, 1H). MS (ISP): 157.7 [M+H]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[CH:16][N:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Br[CH2:22][C:23]1[CH:27]=[CH:26]OC=1>>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][CH:9]([C:12]2[C:20]3[C:15](=[CH:16][N:17]=[CH:18][CH:19]=3)[N:14]([CH2:22][CH2:23][CH2:27][CH3:26])[CH:13]=2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]
Reactant: BrCc1ccoc1
Reactant: CCOC(=O)N1CCC(c2c[nH]c3cnccc23)CC1
Product: CCCCn1cc(C2CCN(C(=O)OCC)CC2)c2ccncc21
Yield: 43 %

Procedure:
This compound was prepared following the procedure described in example 24, part C, starting with 4.9 g (18 mmol) of 4-(1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid ethyl ester and 35.4 ml (21.6 mmol) of a 0.61 M solution of 3-bromomethylfurane. After standard work-up and purification, 6.14 g (43% of yield) of 4-(1-butyl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid ethyl ester were obtained.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7][OH:8].N1C=CN=C1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>CN(C)C=O>[Si:14]([O:8][CH2:7]/[CH:6]=[CH:5]\[CH2:4][CH2:3][CH2:2][Cl:1])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: OC/C=C\CCCCl
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC/C=C\CCCCl
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 92.8 %

Procedure:
98 g of 6-chlorohex-2Z-en-1-ol was dissolved in 250 ml of dimethylformamide and treated with 68 g of imidazole and 113 g of t-butyldimethylsilyl chloride. After stirring 1.5 hours at room temperature, the reaction mixture was poured into ice water and extracted twice with 300 ml of ether. The ethereal solution was washed with 5% hydrochloric acid, aqueous sodium bicarbonate and brine. After drying over potassium carbonate the solvent was evaporated and the residue distilled to give 168.1 g of 6-chlorohex-2Z-en-1-ol t-butyldimethylsilyl ether, bp 95°-100° C./0.4 mm.
Reaction SMILES: [Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:47])C=1>C(Cl)Cl>[Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N+:35]([O-:47])[CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc(C[C@@H]2CC[C@H]([C@H](O[Si](C)(C)C(C)(C)C)c3cccnc3)N2C(=O)OC(C)(C)C)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COC(=O)c1ccc(C[C@@H]2CC[C@H]([C@H](O[Si](C)(C)C(C)(C)C)c3ccc[n+]([O-])c3)N2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Yield: 99.6 %

Procedure:
A solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(pyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (1.15 g, 2.127 mmol) in DCM (22 mL) was cooled to 0° C. and m-CPBA (0.953 g, 4.25 mmol) was added. The reaction was warmed to room temperature. After 2 hours the reaction was quenched with aqueous sodium bisulfite (20 mL). The reaction was then diluted with EtOAc (150 mL) and washed vigorously with aqueous sodium bisulfite (3×40 mL). The organics were washed with brine (2×40 mL), saturated aqueous NaHCO3 (3×40 mL) and then brine (2×40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(1-oxidopyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (1.18 g, 100%). LC-MS=557.2 (M+1)+.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.[CH3:34][N:35]1[CH:40]=[CH:39][C:38](OS(C(F)(F)F)(=O)=O)=[CH:37][C:36]1=[O:49]>>[CH3:1][O:2][CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:38]3[CH:39]=[CH:40][N:35]([CH3:34])[C:36](=[O:49])[CH:37]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1
Reactant: Cn1ccc(OS(=O)(=O)C(F)(F)F)cc1=O
Reactant: COC[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)C(=O)O1
Product: COC[C@]1(c2ccccc2)CCN([C@@H](C)c2ccc(-c3ccn(C)c(=O)c3)cc2)C(=O)O1

Procedure:
The title compound was prepared from (R)-6-(methoxymethyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and trifluoro-methanesulfonic acid 1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl ester following a procedure analogous to that described in Example 76. Mass spectrum (ESI+): m/z=433 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[C:42]([F:45])([F:44])[F:43])=[CH:32][C:31]=2[C:46](=O)/[CH:47]=[CH:48]/N(C)C)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.[NH:53]([CH:55]1[CH2:58][N:57]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:56]1)[NH2:54].C(=O)([O-])O.[Na+]>C(O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:9])=[O:10])[C:5]([F:28])=[CH:4][C:3]=1[O:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:42]([F:43])([F:44])[F:45])=[CH:32][C:31]=1[C:46]1[N:53]([CH:55]2[CH2:56][N:57]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:58]2)[N:54]=[CH:48][CH:47]=1
Reactant: COc1ccc(CN(c2nncs2)S(=O)(=O)c2cc(Cl)c(Oc3ccc(-c4ccccc4C(F)(F)F)cc3C(=O)/C=C/N(C)C)cc2F)c(OC)c1
Reactant: CC(C)(C)OC(=O)N1CC(NN)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: COc1ccc(CN(c2nncs2)S(=O)(=O)c2cc(Cl)c(Oc3ccc(-c4ccccc4C(F)(F)F)cc3-c3ccnn3C3CN(C(=O)OC(C)(C)C)C3)cc2F)c(OC)c1
Temperature: 70 °C
Yield: 266.6 %

Procedure:
(5-Chloro-N-(2,4-dimethoxybenzyl)-4-({3-[(2E)-3-(dimethylamino)prop-2-enoyl]-2′-(trifluoromethyl)biphenyl-4-yl}oxy)-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 44, 563 mg, 0.724 mmol) in ethanol (10 mL) was slowly added a solution of tert-butyl 3-hydrazinoazetidine-1-carboxylate (Preparation 36, 603 mg, 3.22 mmol) in ethanol (10 mL) and acetic acid (0.25 mL) at 0° C. under nitrogen. The reaction was heated to 70° C. for 3 hours and then cooled to room temperature. The reaction mixture was neutralised to pH7 with saturated aqueous sodium hydrogen carbonate solution (2.0 mL) and concentrated in vacuo to afford a yellow oil. The oil was partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was then extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (2×100 mL) dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil (1.74 g). The oil was partially purified by silica gel column chromatography (0%-10% methanol in dichloromethane gradient elution) to afford the title compound as a solid (228 mg) of 52% purity via LCMS. The compound was used without further purification in the next step.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH:4]([CH2:5]COC)[CH:3]1[C:9]([O-:11])=[O:10].[OH-:13].[Na+]>CC(C)=O>[CH3:12][C:2]1([CH3:1])[C@H:4]([CH:5]=[O:13])[C@H:3]1[C:9]([O:11][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:10]
Reactant: [OH-]
Reactant: COCCC1C(C(=O)[O-])C1(C)C
Agent: [Na+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)[C@@H]1[C@@H](C=O)C1(C)C

Procedure:
A solution of 45.26 g of the product of Step A, 50 ml of 2N sodium hydroxide solution and 450 ml of acetone was stirred for 6 hours at 20° C. and was evaporated to dryness. The residue was added to water and ether and the decanted aqueous phase was extracted with ether. The combined organic phases were evaporated to dryness under reduced pressure and the residue was chromatographed over silica gel. Elution with a 4-1 hexane-ethyl acetate mixture yielded 28.75 g of tert.-butyl (1R,trans) 2,2-dimethyl-3-formyl-cyclopropane-carboxylate.
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][O:6][CH3:7])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]=[C:16]=[O:17]>C1(C)C(C)=CC=CC=1>[CH3:1][NH:2][C:3]([N:5]([O:6][CH3:7])[C:16]([NH:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[F:8])=[O:17])=[O:4]
Reactant: O=C=Nc1ccccc1F
Reactant: CNC(=O)NOC
Solvent: Cc1ccccc1C
Product: CNC(=O)N(OC)C(=O)Nc1ccccc1F

Procedure:
To 35 g (0.27 mol) of 1-methyl-3-methoxy urea in 150 ml xylene was added dropwise a solution of 37 g (0.27 mol) 2-fluorophenylisocyanate in 100 ml of xylene. The reaction mixture was refluxed for 4 hours. The reaction mixture was filtered while warm to remove a small amount of triethylamine hydrochloride (impurity in the urea reactant). The filtrate was evaporated to give the biuret product as a solid (m.p. 144°-147° C after recrystallization from benzene). Elemental analysis for fluorine showed: calc. 7.88%, found 7.64%.
Reaction SMILES: [H-].[Na+].[CH2:3]=[C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][C:11]([O:17][CH3:18])=[CH:12][CH:13]=3)[C:8]=2[CH2:7][CH2:6][N:5]1[C:19]([CH:21]1[CH2:23][CH2:22]1)=[O:20].CN(C=[O:28])C>>[CH:21]1([C:19]([N:5]2[CH2:6][C:7]3[C:8](=[O:28])[C:9]4[CH:10]=[C:11]([O:17][CH3:18])[CH:12]=[CH:13][C:14]=4[NH:15][C:16]=3[C:4]2=[CH2:3])=[O:20])[CH2:22][CH2:23]1
Reactant: CN(C)C=O
Reactant: C=C1c2[nH]c3ccc(OC)cc3c2CCN1C(=O)C1CC1
Agent: [H-]
Agent: [Na+]
Product: C=C1c2[nH]c3ccc(OC)cc3c(=O)c2CN1C(=O)C1CC1
Reaction time: 48 h
Yield: 38 %

Procedure:
NaH (1.2 eq; 60% suspension in oil) is added to a solution of 1-methylene-2-cyclopropylcarbonyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (500 mg; 1.7 mmol) in DMF (5 ml). The mixture is stirred under an oxygen atmosphere for 48 hours, further NaH (1.1 eq) is then added and stirring is continued overnight. The DMF is then distilled off under reduced pressure. The crude product is taken up in water and then filtered off. Saturated NH4Cl solution is added to the aqueous phase. The mixture is stirred for 30 minutes. The precipitate is filtered off and then washed successively with water, an MeOH/CH2Cl2 mixture (10/90), acetone and then ethyl acetate. After drying, 2-cyclopropylcarbonyl-7-methoxy-3-methylene-9-oxo-1,3,4,9-tetrahydropyrrolo[3,4-b]quinoline is obtained (yield=38%).
Reaction SMILES: O.[NH2:2][NH2:3].[Br:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]([CH2:16][CH2:17][CH2:18]Cl)[C:12](OC)=[O:13]>C(O)C>[NH2:2][N:3]1[CH2:18][CH2:17][CH2:16][CH:11]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[Br:4])[C:12]1=[O:13]
Reactant: COC(=O)C(CCCCl)c1ccccc1Br
Reactant: NN
Solvent: O
Solvent: CCO
Product: NN1CCCC(c2ccccc2Br)C1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of methyl 2-bromophenylacetate (2.0 g) in DMF (5 mL) was added to a suspension of sodium hydride (containing mineral oil at 40%, 384 mg) in DMF (20 mL) under ice-cooling. The reaction solution was stirred for 10 minutes, further stirred at room temperature for 30 minutes and then ice-cooled again. A solution of 1-chloro-3-iodopropane (1.96 g) in DMF (5 mL) was added to the reaction mixture, and the reaction solution was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The resulting organic layer washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a crude product of methyl 2-(2-bromophenyl)-5-chloropentanoate. Hydrazine monohydrate (4 mL) was added to a solution of the resulting crude methyl 2-(2-bromophenyl)-5-chloropentanoate (2.895 g) in ethanol (20 mL), and the reaction solution was stirred at room temperature for three hours. Hydrazine monohydrate (8 mL) was further added to the reaction solution, and the reaction solution was stirred at room temperature for two days. The reaction solution was concentrated under reduced pressure. Saturated sodium bicarbonate water and ethyl acetate and were added to the residue, and the organic layer was separated. The resulting organic layer washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain 1.504 g of the crude purified title compound. The property value of the compound is as follows.
Reaction SMILES: C([Li])CCC.[F:6][C:7]([F:23])([F:22])[C:8]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C:15]1([CH3:21])[OH:20])([OH:13])[C:9]([F:12])([F:11])[F:10].[C:24](Cl)(=[O:28])[C:25]([CH3:27])=[CH2:26]>O1CCCC1>[C:24]([O:20][C:15]1([CH3:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH:14]1[C:8]([OH:13])([C:9]([F:11])([F:10])[F:12])[C:7]([F:22])([F:23])[F:6])(=[O:28])[C:25]([CH3:27])=[CH2:26]
Reactant: C=C(C)C(=O)Cl
Reactant: CC1(O)CCCCC1C(O)(C(F)(F)F)C(F)(F)F
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C=C(C)C(=O)OC1(C)CCCCC1C(O)(C(F)(F)F)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a flame-dried, nitrogen-purged 250 mL 3-neck roundbottom flask with 50 mL pressure-equalizing addition funnel and magnetic stirbar was charged 85 mL n-butyl lithium (136 mmol, 2 equiv., 1.6 M in hexanes). A degassed solution of 12-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan2-yl)-1-methylcyclohexanol (X) (˜68 mmol, 1 eq.) in 50 mL anhydrous tetrahydrofuran was charged to the addition funnel and added to the reaction mixture dropwise at 0° C. over 30 minutes. The reaction mixture was warmed for 15 minutes on a hot water bath to ensure the reaction was complete. The reaction vessel was cooled to 0° C. and 7.46 g methacryloyl chloride (71.4 mmol, 1.05 eq.) was added dropwise and allowed to stir for 15 minutes. The addition funnel was replaced with a reflux condenser and the reaction heated to reflux for 20 hours. After the reaction was complete, it was cooled to 0° C. and quenched with dilute HCl solution until the pH was less than 5.0. The reaction solution was neutralized with saturated aqueous sodium bicarbonate until the pH was greater than 8. The product was extracted into ethyl ether and the organic phase washed sequentially with aqueous sodium bicarbonate, water, and brine and then dried over magnesium sulfate, filtered, concentrated in vacuo, and stored over a small amount of sodium bicarbonate. The crude product mixture was purified via silica gel column chromatography (20:1 hexane:ethyl acetate eluent) to afford 3.08 of 2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1-methylcyclohex-1-yl methacrylate (XII) as a colorless liquid (1 isomer) of only 66% purity. After standing in the refrigerator overnight, 2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1-methylcyclohex-1-yl methacrylate (XII) crystallizes out of the mixture a white crystalline solid.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][CH:12]([NH2:15])[CH2:13][NH2:14])=[CH:3][CH:2]=1.N.Cl[CH2:18]Cl>>[NH:14]1[CH2:13][CH:12]([CH2:11][C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=[CH:2][CH:3]=2)[N:15]=[CH:18]1
Reactant: NCC(N)Cc1ccnc2ccccc12
Reactant: ClCCl
Agent: N
Product: C1=NC(Cc2ccnc3ccccc23)CN1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To 3-Quinolin-4-yl-propane-1,2-diamine (0.080 g, 3.98 mmol) in 5 ml of dry dichloromethane, formidic acid ethyl ester hydrochloride (0.174 g, 7.96 mmol) (Ohme, R. et al. Angew. Chem. Int. Engl. Ed. 1967, 6, 90) was added. The reaction mixture was stirred overnight at room temperature. Aqueous ammonia (2 ml) was added to the reaction mixture and was partitioned between EtOAc (2×5 ml) and water. The organic layer was dried, filtered and concentrated to give 0.084 g (100%) of the product as a syrup.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([C:8]([NH:10][C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23](=O)[O:24]C4C=CC=CC=4)[CH:17]=3)=[C:13]([F:34])[CH:12]=2)=[O:9])[C:4](=[O:35])[N:3]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH3:42][NH:43][CH3:44]>CN1C(=O)CCC1>[CH3:42][N:43]([CH3:44])[C:23](=[O:24])[NH:22][C:18]1[CH:17]=[C:16]([O:15][C:14]2[CH:32]=[CH:33][C:11]([NH:10][C:8]([C:5]3[C:4](=[O:35])[N:3]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[N:2]([CH3:1])[C:6]=3[CH3:7])=[O:9])=[CH:12][C:13]=2[F:34])[CH:21]=[CH:20][N:19]=1
Reactant: Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)Oc4ccccc4)c3)c(F)c2)c(=O)n(-c2ccccc2)n1C
Reactant: CNC
Solvent: CN1CCCC1=O
Product: Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)N(C)C)c3)c(F)c2)c(=O)n(-c2ccccc2)n1C
Temperature: 40 °C
Yield: 27 %

Procedure:
A mixture of phenyl (4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)pyridin-2-yl)carbamate (100 mg, 0.18 mmol), NMP (5 mL) and aqueous dimethylamine (0.045 mL, 33%) was heated at 40° C. for 2 hours. The solvent was evaporated under reduced pressure at 40° C., and then diluted with EtOAc (20 mL). The precipitate was collected by filtration to give the title compound as a white solid (25 mg, 27%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:19][CH2:20][O:21][CH3:22])=[C:7]([CH:18]=1)[CH:8]=[N:9][C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][C:11]=1[OH:17]>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:19][CH2:20][O:21][CH3:22])=[C:7]([C:8]2[O:17][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([CH3:16])[C:10]=3[N:9]=2)[CH:18]=1
Reactant: COCOc1ccc(OC)cc1C=Nc1c(C)cccc1O
Solvent: c1ccccc1
Product: COCOc1ccc(OC)cc1-c1nc2c(C)cccc2o1
Temperature: 25 °C

Procedure:
A solution of 2-[(5-methoxy-2-methoxymethoxybenzylidene)amino]-3-methylphenol (F4) (1.51 g, 5 mmol) and BaMnO4 (5.13 g, 20 mmol) in benzene (50 mL) was refluxed for 5 hours under dry N2 gas flowing. After the reaction mixture was cooled to room temperature, BaMnO4 was removed through Celite and the filtrate was concentrated in vacuo. The black residue was purified by silica gel column chromatography (CHCl3) to afford the objective compound as a pale yellow soild (976 mg, 65%): 1H-NMR (500 MHz, CDCl3) δ2.68 (s, 3H), 3.55 (s, 3H), 3.87 (s, 3H), 5.25 (s, 2H), 7.02 (dd, 1H, J=9.0, 3.0 Hz), 7.15 (d, 1H, J=8.0 Hz), 7.21 (d, 1H, J=9.0 Hz), 7.24 (t, 1H, J=8.0 Hz), 7.42 (d, 1H, J=8.0 Hz), 7.63 (d, 1H, J=3.0 Hz).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH:15]=O)[C:12]2[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=2[S:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N:22]([C:24](=[O:31])[CH:25]1[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]1)[NH2:23].[OH-].[K+]>CO>[C:1]1([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH:15]=[N:23][NH:22][C:24]([C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)=[O:31])[C:12]2[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=2[S:10]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Cc1c(-c2ccccc2)nc2sc3ccccc3n12
Reactant: CN(N)C(=O)C1CCCNC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C(NN=Cc1c(-c2ccccc2)nc2sc3ccccc3n12)c1cccnc1
Yield: 68 %

Procedure:
0.28 g of 2-phenyl-3-formylimidazo[2,1-b]benzothiazole, 0.15 g of N-methylnipecotohydrazide, and 0.1 g of potassium hydroxide were heated and stirred in 20 ml of methanol at 90° C. for 6 hours. After cooling, the desired substance was obtained in an amount of 0.27 g (yield of 68.0%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[N:11][CH3:12].C(O[CH:16]=[N:17][S:18]([CH3:21])(=[O:20])=[O:19])C>O1CCOCC1>[CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]=[CH:10][N:11]([CH3:12])[CH:16]=[N:17][S:18]([CH3:21])(=[O:19])=[O:20]
Reactant: CCOC=NS(C)(=O)=O
Reactant: CN=CNc1ccc(Cl)cc1C
Solvent: C1COCCO1
Product: Cc1cc(Cl)ccc1N=CN(C)C=NS(C)(=O)=O
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a solution of 18.2 g of N-(2-methyl-4-chlorophenyl)-N'-methylformamidine in 60 ml of abs. dioxane are added dropwise at room temperature 15.1 g of N-ethoxymethylenemethanesulphonamide and the solution is stirred for 1 hour at 60° C. The reaction mixture is subsequently concentrated and the crystallised product is recrystallised from toluene, affording the compound of the formula ##STR4## as a white powder with a melting point of 142°-143° C. The following compounds are also prepared in analogous manner: ##STR5##
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[S:10]1[CH:14]=[CH:13][CH:12]=[C:11]1B(O)O>>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:11]2[S:10][CH:14]=[CH:13][CH:12]=2)=[CH:3][CH:4]=1
Reactant: COc1ccc(Br)cc1
Reactant: OB(O)c1cccs1
Product: COc1ccc(-c2cccs2)cc1

Procedure:
p-Bromoanisole and thiophene-2-boronic acid were treated in a manner similar to Reference Example 20-(1) to give 2-(4-methoxyphenyl)thiophene as a pale yellow solid. APCI-Mass m/Z 191 (M+H).
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:21])([F:20])[CH:5]([OH:19])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1.[F:22][C:23]([F:37])([F:36])[C:24]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][CH:28]=1)=[CH:25]Cl.C(O)(=O)C>CN(C)C=O>[F:22][C:23]([F:36])([F:37])[C:24]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][CH:28]=1)=[CH:25][O:19][CH:5]([C:4]([F:20])([F:21])[F:3])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1
Reactant: OC(c1cccc(Oc2ccccc2)c1)C(F)(F)F
Reactant: CCOc1ccc(C(=CCl)C(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CCOc1ccc(C(=COC(c2cccc(Oc3ccccc3)c2)C(F)(F)F)C(F)(F)F)cc1
Temperature: -40 °C
Reaction time: 6 h

Procedure:
Sodium hydride (0.11 g of a 50% dispersion in oil) was added to a stirred solution of α-trifluoromethyl-3-phenoxybenzyl alcohol (0.6 g, prepared according to the method of UK Patent Specification No. 1,561,575) in dry dimethylformamide. After effervescence had subsided, the resulting mixture was added dropwise to a stirred solution of EZ-1,1,1-trifluoro-2-(4-ethoxyphenyl)-3-chloroprop-2-ene (1.12 g) in dry dimethylformamide (10 cm3), the temperature of the reaction mixture being maintained at -40° C. The reaction mixture was then allowed to warm to the ambient temperature, and was stirred for 6 hours. The mixture was acidified with dilute aqueous acetic acid solution and the product extracted into diethyl ether. The combined ethereal layers were dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure. The crude product was purified by column chromatography on a silica gel support, eluting with dichloromethane containing 3% by volume hexane.