Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].[CH3:21][NH:22][C:23]1[CH:28]=[CH:27][C:26](C2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1>>[CH3:21][NH:22][C:23]1[N:24]=[CH:25][C:26]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:27][CH:28]=1
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Reactant: CNc1ccc(C2OC(C)(C)C(C)(C)O2)cn1
Product: CNc1ccc(-c2ccn3c(=O)c(C(=O)OC)cc(C4CC4)c3c2C)cn1
Yield: 106.5 %

Procedure:
Methyl 8-(6-(methylamino)pyridin-3-yl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A from methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.34 mmol) and N-methyl-5-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridin-2-amine (96.2 mg, 0.41 mmol). Purification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1) afforded the title compound as a yellow solid (131.6 mg, 96%).
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@H:7]2[CH2:11][O:10][CH2:9][C@H:8]2[NH2:12])=[CH:4][CH:3]=1.[C@:15]12([CH2:25][S:26]([OH:29])(=[O:28])=[O:27])[C:22]([CH3:24])([CH3:23])[CH:19]([CH2:20][CH2:21]1)[CH2:18][C:16]2=[O:17].O>CC(O)C>[C:15]12([CH2:25][S:26]([OH:29])(=[O:27])=[O:28])[C:22]([CH3:24])([CH3:23])[CH:19]([CH2:20][CH2:21]1)[CH2:18][C:16]2=[O:17].[Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@@H:7]2[CH2:11][O:10][CH2:9][C@@H:8]2[NH2:12])=[CH:4][CH:3]=1
Reactant: CC1(C)C2CC[C@@]1(CS(=O)(=O)O)C(=O)C2
Reactant: N[C@@H]1COC[C@@H]1Oc1ccc(Br)cc1
Solvent: CC(C)O
Solvent: O
Product: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Product: N[C@H]1COC[C@H]1Oc1ccc(Br)cc1
Temperature: 25 °C
Yield: 43 %

Procedure:
A mixture of cis-4-(4-bromophenoxy)tetrahydrofuran-3-amine (191 g, 0.74 mol) and (1S)-(+)-10-camphorsulfonic acid (154.2 g, 0.66 mol) was dissolved in 2-propanol (2.4 L) and water (100 mL) at reflux. The clear solution was allowed to cool to room temperature over 18 hours, and the resulting crystals were isolated, washed and dried to afford the (+)-camphorsulfonic acid salt of (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine (139.2 g, 0.284 mol) with an e.e. (enantiomeric excess) of 85%. Recrystallization from 2-propanol (1.2 L) and water (70 mL) afforded the (+)-camphorsulfonic acid salt of (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine, with an e.e. of 99%. Yield: 113.2 g, 0.23 mol, 31%. 1H NMR (300 MHz, DMSO-d6) δ 0.74 (s, 3H), 1.05 (s, 3H), 1.23 (d, half of AB quartet J=10 Hz, 1H), 1.29 (d, half of AB quartet, J=10 Hz, 1H), 1.76-1.94 (m, 2H), 2.19-2.28 (m, estimated 2H), 2.35 (d, J=14.7 Hz, 1H), 2.66-2.73 (m, estimated 1H), 2.85 (d, J=14.7 Hz, 1H), 3.78-3.84 (m, 2H), 3.96-4.10 (m, 3H), 5.04 (m, 1H), 6.99 (d, J=8.8 Hz, 2H), 7.52 (d, J=9.0 Hz, 2H), 8.23 (br s, 3H). Additional (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine(+)-camphorsulfonic acid salt (13.6 g, 27.7 mmol) from another experiment was added and the combined batch (126.8 g, 0.258 mol) was washed with 2N aqueous sodium hydroxide solution and extracted three times with methylene chloride. The organic layers were combined and concentrated in vacuo, affording (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine as a white solid with an e.e. of 99%. Yield: 65.6 g, 0.254 mmol, 98% for neutralization.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C:13]([C:18](=O)N)(C)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(=O)OI(C1C=CC=CC=1)OC(C(F)(F)F)=O.O.C(#[N:45])C>>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C:13]([NH2:45])([CH3:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C(N)=O)CCCN(C(=O)OCc2ccccc2)C1
Reactant: CC#N
Agent: O=C(OI(OC(=O)C(F)(F)F)c1ccccc1)C(F)(F)F
Solvent: O
Product: CC1(N)CCCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
3-Carbamoyl-3-methyl-piperidine-1-carboxylic acid benzyl ester (500 mg, 1.81 mmol) in acetonitrile (10 mL) was treated with [bis(trifluoroacetoxyl)iodo]benzene (PIFA) (800 mg, 1.86 mmol) and water (2 mL), the mixture was allowed to stir at 25° C. for 3 hours. LCMS showed starting material consumed, the mixture was heated to 70° C. for 30 min to decompose excess PIFA. The mixture was purified by column chromatography (eluting with 30˜50% methanol in dichloromethane) to give 420 mg (93%) of 3-Amino-3-methyl-piperidine-1-carboxylic acid benzyl ester. LCMS (Method K, ESI): RT=0.95 min, m+H=249.0.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:12]([NH2:15])(=[O:14])=[O:13])[CH:5]=[C:6]([CH:10]=[O:11])[C:7]=1[O:8][CH3:9].[N+:16]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)([O-:18])=[O:17]>>[CH:10]([C:6]1[CH:5]=[C:4]([S:12]([NH2:15])(=[O:14])=[O:13])[CH:3]=[C:2]([C:23]2[CH:22]=[CH:21][CH:20]=[C:19]([N+:16]([O-:18])=[O:17])[CH:24]=2)[C:7]=1[O:8][CH3:9])=[O:11]
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Reactant: COc1c(Br)cc(S(N)(=O)=O)cc1C=O
Product: COc1c(C=O)cc(S(N)(=O)=O)cc1-c1cccc([N+](=O)[O-])c1

Procedure:
Proceeding as in Reference 19, but substituting 3-bromo-5-formyl-4-methoxy-benzenesulfonamide and 3-nitrobenzene boronic acid, gave 5-formyl-6-methoxy-3′-nitro-biphenyl-3-sulfonamide.
Reaction SMILES: CS([C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])[N:6]2[N:5]=1)=O.C(N(CC)C(C)C)(C)C.[NH2:30][C:31]1[CH:32]=[C:33]([C:37]([N:39]2[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]2)=[O:38])[CH:34]=[CH:35][CH:36]=1.COCC(O)C>>[CH3:20][O:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:12]1[N:6]2[C:7]([CH:8]=[N:9][C:4]([NH:30][C:31]3[CH:32]=[C:33]([C:37]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)=[O:38])[CH:34]=[CH:35][CH:36]=3)=[N:5]2)=[CH:10][CH:11]=1
Reactant: CN1CCN(C(=O)c2cccc(N)c2)CC1
Reactant: COc1ccccc1-c1ccc2cnc(S(C)=O)nn12
Solvent: COCC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccccc1-c1ccc2cnc(Nc3cccc(C(=O)N4CCN(C)CC4)c3)nn12
Yield: 21.1 %

Procedure:
2-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (125.0 mg, 0.0004350 mol), N,N-Diisopropylethylamine (0.114 mL, 0.000652 mol) and (3-Amino-phenyl)-(4-methyl-piperazin-1-yl)-methanone (0.191 g, 0.000870 mol) were dissolved in 1-Methoxy-2-propanol (1.2 mL, 0.013 mol) and the reaction was irradiated at 300 watts, 180° C. for 40 minutes or until HPLC showed consumption of starting material. The reaction mixture was then reduced en vacuo and the product was isolated and purified by Gilson prep HPLC to afford 40.55 mg of {3-[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-(4-methyl-piperazin-1-yl)-methanone as a lyophilized powder. (M+H)=443.9. 1H NMR (400 MHz, DMSO, d6) δ 9.63 (s, 1H), 8.99 (s, 1H), 7.76 (m, 3H), 7.45 (t, 1H, J=7.12 Hz), 7.30 (t, 1H, 7.84 Hz), 7.18 (d, 1H, J=8.25 Hz), 7.08 (t, 1H, J=7.45 Hz), 6.96 (m, 3H), 4.05 (m, 2H), 3.81 (s, 3H), 3.44 (m, 2H), 3.19 (m, 2H), 2.99 (m, 2H), 2.82 (s, 3H).
Reaction SMILES: [CH2:1]([N:3]1[C:7](=[O:8])[C:6](=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16]C)[N:5]=[C:4]1[CH3:18])[CH3:2].B(Br)(Br)Br>ClCCl>[CH2:1]([N:3]1[C:7](=[O:8])[C:6](=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[OH:16])[N:5]=[C:4]1[CH3:18])[CH3:2]
Reactant: CCN1C(=O)C(=Cc2ccccc2OC)N=C1C
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCN1C(=O)C(=Cc2ccccc2O)N=C1C
Temperature: -40 °C
Yield: 88.4 %

Procedure:
3-Ethyl-3,5-dihydro-5-(2′-methoxybenzylidene)-2-methylimidazol-4-one (1.2 g) was dissolved in dichloromethane (20 ml) and boron tribromide (1.5 ml) was added dropwise while stirring the mixture at −40° C. Thereafter, the mixture was stirred under ice-cooling for 1 hr, poured into ice water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 3-ethyl-3,5-dihydro-5-(2′-hydroxybenzylidene)-2-methylimidazol-4-one (1 g) as red crystals. The crystals and (S)-glycidyl nosylate (1.3 g) were dissolved in dimethylformamide (20 ml) and potassium carbonate (1.38 g) was added. The mixture was heated at 50° C. for 2 hr, poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oily product (1.02 g). This oily product and 4-(naphthalen-2-yl)piperidine were dissolved in methanol (10 ml) and the mixture was refluxed under heating for 2 hr. After cooling, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol) to give the title compound (0.52 g) as an oil.
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]=O)[N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:18]1([N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH2:16][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:15]=2)=[O:9])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1
Reactant: O=Cc1csc(NC(=O)N(C2CCCCC2)C2CCCCC2)n1
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: O=C(Nc1nc(CN2CCOCC2)cs1)N(C1CCCCC1)C1CCCCC1
Yield: 30 %

Procedure:
1,1-Dicyclohexyl-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)urea was prepared in 30% yield (30 mg) as described in general procedure A from 1,1-dicyclohexyl-3-(4-formyl-thiazol-2-yl)urea (101 mg, 0.3 mmol) and morpholine (30 uL, 0.3 mmol) using sodium triacetoxyborohydride as the reducing reagent.
Reaction SMILES: [C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Br:8][C:9]1[C:10]([F:19])=[C:11]2[C:17]([NH2:18])=[CH:16][NH:15][C:12]2=[N:13][CH:14]=1>N1C=CC=CC=1>[Br:8][C:9]1[C:10]([F:19])=[C:11]2[C:17]([NH:18][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:16][NH:15][C:12]2=[N:13][CH:14]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: Nc1c[nH]c2ncc(Br)c(F)c12
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Nc1c[nH]c2ncc(Br)c(F)c12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 62.7 %

Procedure:
Pivaloyl chloride (0.12 mL, 0.98 mmol) was added to 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (0.15 g, 0.65 mmol) in pyridine (5 mL). The reaction was stirred at room temperature for 10 minutes, and then the pyridine was removed. THF (5 mL) and 2N LiOH (3 mL) were added and stirred for 20 minutes. The THF was removed in vacuo, and water (20 mL)was added to the aqueous residue. The solid formed was collected by filtration and dried to give N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pivalamide (0.128 g, 62% yield) as a solid.
Reaction SMILES: [CH2:1]([CH:4]1[C@:9]([C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[N:8]=[C:7]([N:21]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:6]([CH3:37])([CH3:36])[S:5]1(=[O:39])=[O:38])[CH:2]=C.C(=O)(O)[O-:41].[Na+].C(Cl)Cl.[BH4-].[Na+]>CO>[C:24]([O:23][C:22]([N:21]([C:7]1[C:6]([CH3:37])([CH3:36])[S:5](=[O:38])(=[O:39])[CH:4]([CH2:1][CH2:2][OH:41])[C@:9]([C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[N:8]=1)[C:29](=[O:30])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:28])([CH3:25])([CH3:26])[CH3:27]
Reactant: O=C([O-])O
Reactant: C=CCC1[C@@](C)(c2cc([N+](=O)[O-])ccc2F)N=C(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(C)(C)S1(=O)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=N[C@](C)(c2cc([N+](=O)[O-])ccc2F)C(CCO)S(=O)(=O)C1(C)C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 100.3 %

Procedure:
A 3-necked round bottom flask equipped with a mechanical stirrer, Claisen adapter with thermocouple and a nitrogen inlet was charged with tert-butyl N-[(3R)-2-allyl-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]-N-tert-butoxycarbonyl-carbamate (4.00 g, 7.02 mmol, 2.85:1 ratio of diastereomers), sodium bicarbonate (1.180 g, 14.04 mmol), DCM (30 mL) and MeOH (10.00 mL), and the resulting solution was cooled to Tinternal<−65+/−1° C. Ozone was bubbled through the reaction mixture until starting material was consumed according to LCMS (˜1.5 h). The solution was purged with oxygen and then nitrogen, and sodium borohydride (0.531 g, 14.04 mmol) added in one portion. The cooling bath was removed, and the reaction mixture was allowed to warm to RT overnight. 2 mL acetone was added, followed by 10 mL sat. aq.NH4Cl. After stirring for 10 min, 5 mL water was added and the layers were separated. The organic portion was dried over magnesium sulfate, filtered and concentrated in vacuo to provide tert-butyl N-tert-butoxycarbonyl-N-[(3R)-3-(2-fluoro-5-nitro-phenyl)-2-(2-hydroxyethyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (4.04 g, 2.85:1 ratio of diastereomers) as a white solid that was used without further purification. LC/MS (ESI+) m/z=596.2 (M+Na).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]4[CH:15]=[C:16]([CH:26]=[CH:27][CH:28]=4)[CH2:17][NH:18]C(=O)OC(C)(C)C)=[CH:13][C:8]=3[N:7]([CH3:29])[S:6]2(=[O:31])=[O:30])[CH2:3][CH2:2]1.C(Cl)[Cl:33].Cl.CCOC(C)=O>CO>[ClH:33].[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]4[CH:15]=[C:16]([CH2:17][NH2:18])[CH:26]=[CH:27][CH:28]=4)=[CH:13][C:8]=3[N:7]([CH3:29])[S:6]2(=[O:30])=[O:31])[CH2:3][CH2:2]1
Reactant: CN1c2cc(-c3cccc(CNC(=O)OC(C)(C)C)c3)ccc2N(CC2CC2)S1(=O)=O
Reactant: ClCCl
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Product: CN1c2cc(-c3cccc(CN)c3)ccc2N(CC2CC2)S1(=O)=O
Temperature: 25 °C

Procedure:
To a round bottom flask was added tert-butyl {3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}carbamate (23-1) (0.250 g, 0.564 mmol), DCM (2 mL), MeOH (2 mL), and finally a saturated solution of HCl in EtOAc (4N) (0.705 mL, 2.82 mmol). The reaction mixture was then capped and permitted to stir at room temperature for an hour at which point it was concentrated to give 1-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenyl}methanamine hydrochloride (23-2) as a waxy pink solid. HRMS (M+H)+: observed=344.1429, calculated=344.1427.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1.O1CCCC1.Cl[CH2:23][C:24]([O:26][CH3:27])=[O:25].C[O-].[Na+]>C(OCC)(=O)C.C(O)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]2[O:14][CH:23]2[C:24]([O:26][CH3:27])=[O:25])=[CH:11][CH:10]=1
Reactant: COC(=O)CCl
Reactant: O=Cc1ccc(COc2ccccn2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: COC(=O)C1OC1c1ccc(COc2ccccn2)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a mixture of 4-(pyridin-2-yloxymethyl)-benzaldehyde (24.8 g) described in Manufacturing Example 1-1-2 and tetrahydrofuran (160 mL) was added methyl chloroacetate (10.2 mL) at −15° C., and then sodium methoxide (23.7 mL, 28% methanol solution) was added thereto at the same temperature. The reaction mixture was stirred for 1 hour at 0° C., and then stirred for 2 hours at room temperature. The reaction mixture was added to 800 mL of an ice water containing acetic acid (6 mL), and the reaction mixture was warmed to room temperature. Ethyl acetate was added to the reaction mixture for extraction, and then the organic layer was separated, washed with saturated saline, and dried over anhydrous magnesium sulfate. The solvent was evaporated under a reduced pressure to obtain the title compound (30.2 g).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][C:7]2=[O:12].Cl[C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=1.C([O-])([O-])=O.[K+].[K+]>>[O:1]=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[C:7]([O:12][C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=3)=[CH:6][CH:5]=[CH:4][C:3]1=2
Reactant: NC(=O)c1ccc(Cl)nc1
Reactant: O=C1CCCc2c(O)cccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Product: NC(=O)c1ccc(Oc2cccc3c2CCCC3=O)nc1
Yield: 55.3 %

Procedure:
Using a method similar to Intermediate 1, using 5-hydroxy-1-tetralone (2.68 g, 16.5 mmol), 6-chloronicotinamide (2.34 g, 15.0 mmol) and K2CO3 (3.11 g, 22.5 mmol) gives the title compound (2.34 g) as a yellow solid. Mass spectrum (ion spray): m/z=283 (M+1); 1HNMR (DMSO-d6): 8.55 (s, 1H), 8.27 (d, 1H), 8.02 (s, 113), 7.80 (m, 1H), 7.48 (s, 1H), 7.43-7.37 (m, 1H), 7.14 (d, 1H), 2.66 (t, 2H), 2.58 (t, 2H), 1.96 (m, 2H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][N:11]2C(=O)C3=CC=CC=C3C2=O)[CH2:4][CH2:3]1.O.NN>C(O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][NH2:11])[CH2:4][CH2:3]1
Reactant: CN1CCN(CCCN2C(=O)c3ccccc3C2=O)CC1
Agent: NN
Solvent: O
Solvent: CCO
Product: CN1CCN(CCCN)CC1
Reaction time: 1.5 h
Yield: 53.4 %

Procedure:
To a solution of N-[3-(4-methyl-1-piperazinyl)propyl]phthalimide (502 g) in ethanol (3.0 l) was added 100% hydrazine hydrate (187.6 g). The nesulting mixture was refluxed with stiving for 1.5 hours. The reaction mixture was cooled and then filtered. The filter cake was washed with ethanol (1 l). The filtrate and washing were combined and evaporated, under reduced pressure. The residual oil was distilled under reduced pressure to give 3-(4-methyl-1-piperazinyl)propylamine (146.6 g), bp 34 mmHg/127° to 128° C.
Reaction SMILES: C1C=CC(/C=C/[CH2:9][O:10][C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=CC=1.[CH2:22]1[CH:26]2[CH:27]3[CH:31]=[CH:30][CH:29]([CH:25]2[CH:24]=[CH:23]1)[CH2:28]3.[CH:32]1[CH2:36][CH:35]=[CH:34][CH:33]=1>O>[CH3:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:32]=[CH:36][C:35]([OH:10])=[CH:34][CH:33]=1.[CH2:9]=[O:10]
Reactant: C1=CCC=C1
Reactant: OC[C@H]1O[C@@H](OC/C=C/c2ccccc2)[C@H](O)[C@@H](O)[C@@H]1O
Reactant: C1=CC2C3C=CC(C3)C2C1
Solvent: O
Product: C=O
Product: CCCCCCCCCc1ccc(O)cc1
Temperature: 160 °C
Reaction time: 5 h
Yield: 68 %

Procedure:
300 g of rosin are heated to 260° C. in a 3 liter pressure apparatus. 700 g of dicyclopentadiene containing 75% of cyclopentadiene units are metered in within 2 hours, and the mixture is kept at this temperature for a further 5 hours while stirring; during this procedure, the pressure, which initially increased to 9 bar, decreases to 5 bar. The melt is then allowed to cool to 160° C. 710 g of a water-soluble resol obtained from 1,860 g of nonylphenol and 510 g of formaldehyde (processing viscosity 250 mPa.s, residue on drying 68% after heating for one hour at 135° C.) are metered into this cooled melt. With constant removal of water, the mixture is heated to 250° C. and then, on reaching a viscosity of 100 mPa.s of a 50% strength toluene solution at 23° C., down to 50 mbar while distilling off the volatile components. Yield 1402 g, melting point 145° C., acid number 11 mg KOH/g, viscosity of a 40% strength solution in linseed oil at 350 dPa.s/23° C., compatibility with a mineral oil having a low aromatics content and a boiling range of 240°-270° C. and having an aniline point of 72° C. better than 1 : 20, and with an aromatics-free mineral oil having a boiling range of 240°-270° C. and an aniline point of 92° C. 1 : 2. The compatibility with linseed oil is infinite at 23° C. The weight average molecular weight Mw is 7,550.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:9][C:10]([CH2:19][S:20][CH3:21])=[C:11]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[N:12]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:22]C1C=CC=C(C(OO)=[O:30])C=1.C(=O)([O-])O.[Na+]>O1CCCC1>[ClH:22].[F:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:9][C:10]([CH2:19][S:20]([CH3:21])=[O:30])=[C:11]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[N:12]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCc1[nH]c(-c2cccc(F)c2)nc1-c1cccnc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CS(=O)Cc1[nH]c(-c2cccc(F)c2)nc1-c1cccnc1
Product: Cl
Temperature: 25 °C
Reaction time: 5 h
Yield: 78.4 %

Procedure:
To a solution of 2-(3-fluorophenyl)-5-methylthiomethyl-4-(3-pyridyl)imidazole (152 mg) in tetrahydrofuran (10 ml) was added metachloroperbenzoic acid (97 mg, 70% purity) under ice-cooling, and the mixture was stirred at room temperature for 5 hours. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: chloroform:methanol=19:1), and then, treated with hydrogen chloride-dioxane solution to obtain 2-(3-fluorophenyl)-5-methylsulfinylmethyl-4-(3-pyridyl)imidazole hydrochloride (140 mg) as colorless powder.
Reaction SMILES: [C:1]([O:4][CH:5]([CH3:11])[CH2:6][CH2:7][C:8](O)=[O:9])(=[O:3])[CH3:2].C1(C)C=CC=CC=1.C(Cl)(=O)C([Cl:22])=O>CN(C)C=O>[C:1]([O:4][CH:5]([CH3:11])[CH2:6][CH2:7][C:8]([Cl:22])=[O:9])(=[O:3])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(=O)OC(C)CCC(=O)O
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CC(=O)OC(C)CCC(=O)Cl
Temperature: 50 °C
Reaction time: 1 h
Yield: 81.5 %

Procedure:
46.5 g (0.29 mol) of 4-acetoxypentanoic acid are dissolved at room temperature in 230 ml of abs. toluene, and then 0.2 ml of abs. Dimethyl formamide is added. Then 32.6 ml (0.38 mol) of oxalyl chloride are added dropwise such that the evolution of gas remains under control. When the dropwise addition is complete, the reaction mixture is heated to 50° C. and stirred for 1 hour at this temperature. The orange-red reaction solution is concentrated by evaporation. Distillation of the residue gives 42.2 g of 4-acetoxypentanoic acid chloride as a colorless liquid of b.p.34 110°-112° C.
Reaction SMILES: [C:1]1(=O)[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][NH2:17])=[CH:12][CH:11]=1>O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][N:17]=[C:1]2[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]2)=[CH:12][CH:11]=1
Reactant: O=C1CCCC(=O)C1
Reactant: NNc1ccc(Cl)cc1
Solvent: O
Product: O=C1CCCC(=NNc2ccc(Cl)cc2)C1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 1,3-cyclohexanedione (5.05 g, 45 mmol) in water is treated over a 10 min period with an aqueous suspension of p-chlorophenylhydrazine (8.06 g, 45 mmol), stirred at room temperature for 16 h and filtered. The filtercake is washed with water and dried in vacuo to give the title product which is used as in Example 132.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([Cl:14])=[N:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:4][N:3]=1.[CH3:15][NH2:16]>C(Cl)Cl.C1COCC1.CC(C)=O>[Cl:14][C:9]1[C:8]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([CH2:15][NH2:16])[N:7]=2)=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: Clc1ncnc(-c2cccnc2Cl)n1
Reactant: CN
Solvent: C1CCOC1
Solvent: CC(C)=O
Solvent: ClCCl
Product: NCc1ncnc(-c2cccnc2Cl)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To 2-chloro-4-(2-chloro-pyridin-3-yl)-[1,3,5]triazine (10.0 g, 44.0 mmol) in 55 ml of methylene chloride was added methylamine (45 ml, 88.0 mmol) as a 2.0 M solution in THF at 0° C. After stirring at room temperature for 18 h, the mixture was diluted with acetone and filtered through a plug of silica gel and concentrated to yield the desired product. MS m/z=222 [M+H]+. Calc'd for C9H8ClN5: 221.65.