Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]([CH3:23])=[C:18]([CH2:20][CH2:21][OH:22])[N:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:31]([Si:35](Cl)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([CH3:34])([CH3:33])[CH3:32]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]([CH3:23])=[C:18]([CH2:20][CH2:21][O:22][Si:35]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1oc(-c2ccc(OCc3ccccc3)cc2)nc1CCO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1oc(-c2ccc(OCc3ccccc3)cc2)nc1CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 6 h
Yield: 99.6 %

Procedure:
To a mixture of 2-[2-(4-Benzyloxy-phenyl)-5-methyl-oxazol-4-yl]-ethanol [CAS 403611-91-6] (4.04 g, 13.0 mmol), triethylamine (3.6 mL, 25 mmol, and DMAP (0.16 g, 1.3 mmol) in CH2Cl2 (80 mL) at 0° C. is added a solution of tert-butylchlorodiphenylsilane (3.95 g, 14.4 mmol) in CH2Cl2 (10 mL) drop wise. The mixture is warmed to room temperature and stirred for 6 h. The mixture is washed with 0.5 N HCl (80 mL), and the organic phase is dried (MgSO4). After the solvent is removed in vacuo, the residue is purified by flash chromatography (elute 2:1 hexanes:EtOAc) to yield 7.09 g of the title compound as a white solid. MS (ES+) 548
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[OH:14])[CH2:5][C@@H:6]([C:8]([OH:10])=[O:9])[NH2:7].C(=O)([O-])[O-].[Na+].[Na+].[C:21](ON1C(=O)CCC1=O)([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22]>O1CCOCC1.O.O1CCOCC1>[C:21]([NH:7][C@H:6]([C:8]([OH:10])=[O:9])[CH2:5][C:4]1[CH:11]=[CH:12][C:13]([OH:14])=[C:2]([Cl:1])[CH:3]=1)([O:23][CH2:24][CH:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:32]2[C:37]1=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:22]
Reactant: O=C(OCC1c2ccccc2-c2ccccc21)ON1C(=O)CCC1=O
Reactant: N[C@@H](Cc1ccc(O)c(Cl)c1)C(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: O=C(N[C@@H](Cc1ccc(O)c(Cl)c1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Temperature: 0 °C
Reaction time: 5 h

Procedure:
3-chlorotyrosine* (Aldrich 51,244-3)(113.5 g, 526 mmol) was added to a roundbottom flask equipped with a mechanical stirrer and temperature probe. 3-chlorotyrosine was dissolved in a solution of dioxane:water 2:1 (500 mL). Sodium carbonate (55.8 g, 526 mmol) was added, and the solution cooled to 0° C. in an ice bath. Fmoc-OSu (177.5 g, 526 mmol) was dissolved in dioxane (300 mL) and added in one portion to the solution at 0° C. The reaction was stirred for 5 hours at 0° C. The reaction was allowed to warm to room temperature overnight. The reaction was concentrated until a volume of 100 mL was achieved. 0.5 M potassium hydrogensulfate was added until the pH was 3. The pH was determined using pH paper (0-14) that was placed directly into the mixture. The pH was determined by comparison to the chart included with the pH paper. The solution was extracted with ethyl acetate (3×500 mL). The organic layers were combined and washed with water (500 mL) and brine (500 mL). The organic layer was then washed over sodium sulfate and concentrated to a constant eight (under vacuum) to give Fmoc-3-chlorotyrosine as a light beige solid. (204 g, 95% purity by area)
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([F:27])[C:7]3[NH:11][C:10](=[O:12])[N:9]([CH:13]4[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]4)[C:8]=3[CH:26]=2)[CH2:3][CH2:2]1.[ClH:28]>ClCCl.O1CCOCC1>[ClH:28].[CH:1]1([C:4]2[CH:5]=[C:6]([F:27])[C:7]3[NH:11][C:10](=[O:12])[N:9]([CH:13]4[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]4)[C:8]=3[CH:26]=2)[CH2:2][CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(n2c(=O)[nH]c3c(F)cc(C4CC4)cc32)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=c1[nH]c2c(F)cc(C3CC3)cc2n1C1CCNCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1,1-Dimethylethyl 4-(6-cyclopropyl-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate (D28, 0.28 mmol, 107 mg) was dissolved in 1 ml of dichloromethane and treated with HCl (1 ml of a 4M solution in 1,4-dioxane) at room temperature and the mixture stirred at room temperature for 3 hours. The solvent was evaporated to afford the title compound, 100 mg, 0.32 mmol, complete conversion, M++H=276.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:4]([NH:13][C@H:14]2[CH2:18][CH2:17][CH2:16][C@@H:15]2[NH2:19])=[N:5][CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[N:8]=1.[N:20]1[N:21]([C:25]2[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=2[C:27](O)=[O:28])[N:22]=[CH:23][CH:24]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[Cl:2][C:3]1[C:4]([NH:13][C@H:14]2[CH2:18][CH2:17][CH2:16][C@@H:15]2[NH:19][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=2[N:21]2[N:22]=[CH:23][CH:24]=[N:20]2)=[N:5][CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[N:8]=1
Reactant: O=C(O)c1ccccc1-n1nccn1
Reactant: N[C@H]1CCC[C@@H]1Nc1ncc(C(F)(F)F)nc1Cl
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(N[C@H]1CCC[C@@H]1Nc1ncc(C(F)(F)F)nc1Cl)c1ccccc1-n1nccn1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a solution of (1S,2S)-1-N-[3-chloro-5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (530 mg, 1.67 mmol) in dry DMF (5.6 ml) was added 2-(2H-1,2,3-triazol-2-yl)benzoic acid (CAS number 1001401-62-2; 348 mg, 1.84 mmol), HATU (953 mg, 2.51 mmol) and triethylamine (699 μl, 5.01 mmol) and then stirred at room temperature for 17 hours. The reaction was partitioned between ethyl acetate and a saturated solution of sodium bicarbonate. The organics were washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol) to afford the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][CH:15]1[C:24]2[C:19](=[CH:20][C:21]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:16]3[CH2:17][CH2:18][C:19]4[C:24](=[CH:23][CH:22]=[C:21]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)[CH:20]=4)[CH:15]3[CH3:14])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: CC1NCCc2cc(N3CCOCC3)ccc21
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Product: CC1c2ccc(N3CCOCC3)cc2CCN1C(=O)c1cc2ncc(Br)cn2n1

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 1-Methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: Br[C:2]1[C:3](=[O:21])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([F:20])[C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=1.[NH2:22][C@@H:23]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:24]([CH3:27])[CH2:25][OH:26].CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[Br:8][C:6]1[N:7]=[C:2]([NH:22][C@@H:23]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH3:27])[CH2:25][OH:26])[C:3](=[O:21])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([F:20])[C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=1
Reactant: COC(=O)c1cc(F)c(C)c(-n2cc(Br)nc(Br)c2=O)c1
Reactant: C[C@@H](CO)[C@@H](N)c1ccccc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(F)c(C)c(-n2cc(Br)nc(N[C@@H](c3ccccc3)[C@@H](C)CO)c2=O)c1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-5-fluoro-4-methylbenzoate (Example 252 g, 0.9 g) in THF (3 mL) was added (2R,3R)-3-amino-2-methyl-3-phenylpropan-1-ol (Example 328a, 0.389 g) and Hunig's Base (0.374 mL) and the reaction stirred at 50° C. for 8 h. The reaction mixture was diluted with ethyl acetate and washed with aqueous NaHCO3. The organics were dried (MgSO4) and concentrated in vacuo to leave the crude product which was triturated overnight in 2:1 isohexane/diethyl ether to give the subtitle compound. Purification of the filtrate (SiO2 chromatography eluting with 50-100% diethyl ether in isohexane) to give further subtitle compound (total 0.820 g).
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]=1Cl)=[O:13])[CH2:8]2.[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]=1[N:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:13])[CH2:8]2
Reactant: O=C(NC1C2CC3CC(C2)CC1C3)c1cnn(-c2ccccc2)c1Cl
Reactant: C1CCNC1
Product: O=C(NC1C2CC3CC(C2)CC1C3)c1cnn(-c2ccccc2)c1N1CCCC1

Procedure:
Phenyl-5-pyrrolidin-1-y1-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide was prepared using Procedure A from 5-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (Intermediate 3) and pyrrolidine. Mass spectrum (ES) MH+=391.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[NH:18][C:17](=[O:19])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1.[CH3:20][O:21]C1C=C(OC)C=CC=1C=O>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:21][CH3:20])[CH:6]=[CH:5][C:4]=1[C:9]1[NH:18][C:17](=[O:19])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1
Reactant: COc1ccc(C=O)c(OC)c1
Reactant: COc1ccccc1-c1nc2ccccc2c(=O)[nH]1
Product: COc1ccc(-c2nc3ccccc3c(=O)[nH]2)c(OC)c1
Yield: 84.3 %

Procedure:
According to the preparation of 42, 2,4-dimethoxybenzaldehyde (37) (1.2 g, 7.3 mmol) was used to afford 46 (1.7 g, 84.3%) as pale yellow needles.
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[NH2:24])[C:17]([O:19][CH3:20])=[O:18].O>C1COCC1>[CH3:20][O:19][C:17]([C:16]1[CH:21]=[CH:22][C:23]2[NH:24][C:1](=[O:2])[NH:13][C:14]=2[CH:15]=1)=[O:18]
Reactant: COC(=O)c1ccc(N)c(N)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1ccc2[nH]c(=O)[nH]c2c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 1,1′-carbonyldiimidazole (5 g) in THF (20 ml) was added to a solution of methyl 3,4-diaminobenzoate (CAS Reg. No. 36692-49-6, 5 g) in THF (50 ml). The mixture was stirred at room temperature for 2 h. Water (150 ml) was added. The mixture was filtered and the residue dried to give the title compound (5.6 g) as a light yellow powder. MS (m/e, ISP neg. ion)=191.2 [M−H+].
Reaction SMILES: [OH-].[Na+].[CH:3]([CH:6]([C:14]#[N:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])([CH3:5])[CH3:4].[CH2:16](Cl)[CH:17]=[CH2:18]>O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:18]([C:6]([C:14]#[N:15])([CH:3]([CH3:5])[CH3:4])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])[CH:17]=[CH2:16]
Reactant: Cc1ccccc1C(C#N)C(C)C
Reactant: C=CCCl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Product: C=CCC(C#N)(c1ccccc1C)C(C)C
Temperature: 40 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
To a solution of 362 g of sodium hydroxide in 362 ml of demineralized water 216.6 g of α-isopropyl-2-methylbenzyl cyanide and 6.4 g of tetrabutylammonium hydrogen sulfate were added, and the mixture was heated to 40° C. with intensive stirring. During 3hours 287 g of allylchloride was added. During, the addition and for further two hours the temperature of the reaction mixture was maintained at 40° C. and thereafter at 60° C. for additional three hours. After cooling to room temperature, the reaction mixture was diluted with 550 ml of water and the product was extracted into toluene. After washing with water until neutral pH and drying with anhydrous magnesium sulfate, the solvent was evaporated and the residue was distilled under diminished pressure to obtain 249 g (93%) of the desired compound, b.p. 122°-124 ° C./333 Pa.
Reaction SMILES: C1C2NC3C(=CC=CC=3)SC=2C=CC=1.[CH2:15](Br)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C1CCN2C(=NCCC2)CC1.[CH2:35]([O:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)=[CH:48][CH:47]=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH:43]=[CH2:44]>CN(C)C=O>[CH2:35]([O:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:57][CH2:56][N:55]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:54][CH2:53]2)=[CH:48][CH:47]=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH:43]=[CH2:44]
Reactant: CCCCCCCCBr
Reactant: C=CCCCCCCCCOc1ccc(N2CCNCC2)cc1
Agent: c1ccc2c(c1)Nc1ccccc1S2
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: C=CCCCCCCCCOc1ccc(N2CCN(CCCCCCCC)CC2)cc1
Temperature: 0 °C

Procedure:
A total of 0.2 g of a polymerization inhibitor (phenothiazine) was dissolved in N,N-dimethylformamide. To the resulting solution were added and dissolved 0.62 g (0.0032 mol) of octyl bromide, 2.5 g (0.016 mol) of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), and 1 g (0.0032 mol) of the above-prepared 1-[4-(9-decenyloxy)phenyl]piperazine, followed by a reaction at 60° C. in an atmosphere of nitrogen gas for 48 hours with stirring. After completion of the reaction, the solution was poured into ice water, extracted with two portions of 300 mL of diethyl ether, washed with 300 mL of distilled water and dehydrated over anhydrous sodium sulfate overnight. After filtration, the solution was diluted with hexane and separated into soluble matters and insoluble matter. The hexane-soluble matter was then recrystallized from ether and hexane (1:3) and thereby yielded the target compound, 1-[4-(9-decenyloxy)phenyl]-4-octylpiperazine.
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:11]=[C:12]([C:13]([OH:15])=O)[C:7]=2[CH:6]=[N:5]1)[CH3:3].[NH2:22][CH2:23][C:24]1[C:25](=[O:34])[NH:26][C:27]([CH3:33])=[CH:28][C:29]=1[CH:30]1[CH2:32][CH2:31]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH:30]1([C:29]2[CH:28]=[C:27]([CH3:33])[NH:26][C:25](=[O:34])[C:24]=2[CH2:23][NH:22][C:13]([C:12]2[C:7]3[CH:6]=[N:5][N:4]([CH:2]([CH3:1])[CH3:3])[C:8]=3[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:11]=2)=[O:15])[CH2:31][CH2:32]1
Reactant: Cc1cc(C2CC2)c(CN)c(=O)[nH]1
Reactant: CC(C)n1ncc2c(C(=O)O)cc(-c3ccncc3)nc21
Agent: On1nnc2cccnc21
Solvent: CN1CCOCC1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: Cc1cc(C2CC2)c(CNC(=O)c2cc(-c3ccncc3)nc3c2cnn3C(C)C)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-(1-Methylethyl)-6-(4-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (100 mg, 0.354 mmol), 3-(aminomethyl)-4-cyclopropyl-6-methyl-2(1H)-pyridinone (104 mg, 0.354 mmol), EDC (81 mg, 0.425 mmol), HOAt (48 mg, 0.354 mmol), and N-methylmorpholine (0.156 mL, 1.42 mmol) were suspended in DMF(5 mL) and stirred at room temperature overnight. The contents were filtered, washed with ethanol, and then concentrated in vacuo. The crude solid was purified by reverse phase HPLC (mobile phase: 20-40%, ACN in H2O, 0.1% TFA). The isolated solid was then neutralized with saturated NaHCO3, and washed with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to afford the title compound as an off-white solid, 0.042 g (26%). LCMS E-S (M+H)=443.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.71-0.78 (m, 2 H), 0.94 (dd, J=8.34, 2.27 Hz, 2 H), 1.57 (d, J=6.57 Hz, 6 H), 2.12 (s, 3 H), 2.13-2.18 (m, 1 H), 4.62 (d, J=4.80 Hz, 2 H), 5.38 (s, 1 H), 5.54 (s, 1 H), 8.37 (s, 1 H), 8.44-8.54 (m, 3 H), 8.91 (d, J=6.06 Hz, 2 H), 9.04 (s, 1 H), 11.51 (br. s., 1 H).
Reaction SMILES: [CH:1]1([S:4]([N:7]2[CH2:12][CH2:11][CH:10]([CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19]([OH:21])=O)[CH2:9][CH2:8]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH2:25][CH:26]1[CH:33]2[CH2:34][C:29]3([OH:36])[CH2:30][CH:31]([CH2:35][CH:27]1[CH2:28]3)[CH2:32]2>>[CH:1]1([S:4]([N:7]2[CH2:8][CH2:9][CH:10]([CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19]([NH:25][CH:26]3[CH:27]4[CH2:35][CH:31]5[CH2:30][C:29]([OH:36])([CH2:34][CH:33]3[CH2:32]5)[CH2:28]4)=[O:21])[CH2:11][CH2:12]2)(=[O:5])=[O:6])[CH2:3][CH2:2]1
Reactant: NC1C2CC3CC1CC(O)(C3)C2
Reactant: O=C(O)c1cccc(OCCC2CCN(S(=O)(=O)C3CC3)CC2)c1
Product: O=C(NC1C2CC3CC1CC(O)(C3)C2)c1cccc(OCCC2CCN(S(=O)(=O)C3CC3)CC2)c1

Procedure:
Prepared from 3-[2-(1-cyclopropanesulfonyl-piperidin-4-yl)-ethoxy]-benzoic acid and 4-amino-1-hydroxyadamantane. 1H NMR (400 MHz, CDCl3): δ 7.32-7.38 (m, 2H), 7.24-7.26 (m, 1H), 7.03 (dd, 1H), 6.32 (d, 1H), 4.19-4.24 (m, 1H), 4.07 (t, 2H), 3.78-3.85 (m, 2H), 2.81 (td, 2H), 2.61 (br. s., 2H), 2.22-2.29 (m, 3H), 2.18-2.22 (m, 1H), 1.95 (d, 2H), 1.73-1.89 (m, 11H), 1.65-1.73 (m, 1H), 1.59 (d, 2H), 1.41 (dd, 1H), 1.35 (dd, 1H), 1.14-1.20 (m, 2H), 0.94-1.00 (m, 2H).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[C:12]([CH3:13])=[C:11]([CH3:14])[NH:10][CH:9]=1)=[O:7])[CH3:4].Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=[CH:18][CH:17]=1.O>CN(C)C=O>[CH2:3]([O:5][C:6]([C:8]1[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[CH:9]=1)=[O:7])[CH3:4]
Reactant: CCOC(=O)c1c[nH]c(C)c1C
Reactant: Clc1ccnc2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(-c2ccnc3ccccc23)c(C)c1C
Temperature: 40 °C
Reaction time: 0.3 h

Procedure:
0.285 g (8.9 mmol) of sodium hydride, at 75% by weight in liquid petroleum jelly, is added at a temperature in the region of 20° C. under an argon atmosphere to a solution of 1.35 g (8.1 mmol) of 3-ethoxycarbonyl-4,5-dimethyl-1H-pyrrole in 8 mL of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.3 hour, 1.45 g (8.9 mmol) of 4-chloroquinoline and 2 mL of dimethylformamide are added. After stirring at a temperature in the region of 140° C. for 6 hours, the reaction mixture is poured into 100 mL of salt water and then extracted with twice 50 mL of ethyl acetate. The combined organic phases are washed with 15 mL of water, carefully separated by settling and then concentrated to dryness under reduced pressure (2.7 kPa) to give a brown oil which is purified by silica gel chromatography [eluent: cyclohexane/ethyl acetate (75/25 by volume)]. After concentrating the fractions under reduced pressure (2.7 kPa), 1.32 g of 3-ethoxycarbonyl-4,5-dimethyl-1-(quinol-4-yl)-1H-pyrrole are obtained in the form of a yellowish oil. 1H NMR spectrum (300 MHz, d6-(CD3)2SO, δ in ppm): 1.27 (t, J=7 Hz, 3H), 1.87 (s, 3H), 2.27 (s, 3H), 4.21 (mt, 2H), 7.37 (dd, J=8 and 1 Hz, 1H), 7.55 (s, 1H), 7.62 (d, J=5 Hz, 1H), 7.70 (ddd, J=8, 7 and 1 Hz, 1H), 7.89 (ddd, J=8, 7 and 1 Hz, 1H), 8.19 (broad d, J=8 Hz, 1H), 9.07 (d, J=5 Hz, 1H).
Reaction SMILES: [O:1]1CCO[CH:2]1[CH2:6][CH2:7][N:8]1[C:13]2=[N:14][C:15]([O:18][CH3:19])=[CH:16][N:17]=[C:12]2[CH:11]=[CH:10][C:9]1=[O:20].Cl>O1CCCC1>[CH3:19][O:18][C:15]1[N:14]=[C:13]2[N:8]([CH2:7][CH2:6][CH:2]=[O:1])[C:9](=[O:20])[CH:10]=[CH:11][C:12]2=[N:17][CH:16]=1
Reactant: COc1cnc2ccc(=O)n(CCC3OCCO3)c2n1
Agent: Cl
Solvent: C1CCOC1
Product: COc1cnc2ccc(=O)n(CCC=O)c2n1
Temperature: 50 °C
Reaction time: 4 h
Yield: 87.6 %

Procedure:
5-[2-(1,3-Dioxolan-2-yl)ethyl]-3-methoxypyrido[2,3-b]pyrazin-6(5H)-one (397 mg, 1.43 mmol) was dissolved in tetrahydrofuran (15 ml). To the solution was added a 1N hydrochloric acid aqueous solution (5 ml) under cooling on ice and the mixture was stirred at room temperature for two and a half hours and at 50° C. for 4 hours. After cooling in the air, the solvent was removed under reduced pressure and the residue was alkalized by adding saturated sodium bicarbonate water under cooling on ice. The resultant was extracted with dichloromethane, the extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield 292 mg (87%) of the title compound in the form of a yellowish solid.
Reaction SMILES: [Cl-].CS(C)=O.[CH3:6][O:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)=[C:10]([CH2:25][CH2:26][CH2:27][OH:28])[CH:9]=1.C(N(CC)CC)C>C(Cl)Cl>[CH:27]([CH2:26][CH2:25][C:10]1[CH:9]=[C:8]([O:7][CH3:6])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]=1[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)=[O:28]
Reactant: COc1cc(CCCO)c(OC2CCCCO2)c2ccccc12
Agent: [Cl-]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(CCC=O)c(OC2CCCCO2)c2ccccc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.3 %

Procedure:
An oven-dried 25 ml 2-necked (14/20) round bottom flask, equipped with magnetic stirring bar, nitrogen inlet and serum cap, is charged with a solution of oxalkyl chloride (61 μl) in 2 ml methylene chloride. This solution is placed under a nitrogen atmosphere and cooled to -60° C. to -50° C. Dimethylsulfoxide (99 μl) is added (neat) dropwise to give a colorless solution. After 2-3 min a solution of 3-[4-methoxy-1-[(tetrahydro-2H-pyran-2-yl)oxy]-2-naphthalenyl]-1-propanol (0.19 g) in 1 ml methylene chloride is added drowpise. The resulting mixture is stirred at -60° C. to -50° C. for 15 min and then treated with triethylamine (0.44 ml). This gives rise to a yellow colored milky suspension. The cooling bath is removed and the stirred mixture is allowed to warm to room temperature at which time the mixture is diluted with water and extracted with ether. The organic phase is washed three times with water (after adjusting the pH to 7 with 10% aqueous sodium bisulfate), dried with magnesium sulfate, filtered and concentrated to give 0.18 g of the crude title compound as an orange colored oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[Zn]I.[N+:10]([C:13]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=1[CH:15]=[O:16])([O-:12])=[O:11].C[Si](Cl)(C)C.Cl>C1COCC1.[Cl-].[Cl-].[Cl-].[Cr+3]>[N+:10]([C:13]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=1[C:15]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])=[O:16])([O-:12])=[O:11]
Reactant: O=Cc1cc(F)ccc1[N+](=O)[O-]
Reactant: Clc1ccccc1[Zn]I
Agent: [Cr+3]
Agent: C[Si](C)(C)Cl
Agent: Cl
Solvent: C1CCOC1
Product: O=C(c1ccccc1Cl)c1cc(F)ccc1[N+](=O)[O-]
Temperature: 65 °C
Reaction time: 18 h

Procedure:
To 2.6 g of chromium trichloride suspended in 50 ml of THF are successively added 30 ml of a 0.5M solution in THF of 2-chlorophenyliodozinc, 2.54 g of 2-nitro-5-fluorobenzaldehyde and 5.7 ml of trimethylsilyl chloride. The mixture is heated at 65° C. for 1 hour and then left at room temperature for 18 hours. 1M hydrochloric acid solution is added to the reaction medium, the precipitate formed is filtered off and the filtrate is concentrated. The residue is taken up in ethyl acetate and washed with water. The organic phase is dried over anhydrous sodium sulfate and concentrated. The residue is chromatographed on a column of silica gel, eluting with cyclohexane, to give 1 g of the expected product.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11]([CH3:14])[C:10]=2[NH2:15])=[CH:5][CH:4]=1.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[NH:13][N:12]=[C:11]([CH3:14])[C:10]=2[NH:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2[nH]nc(C)c2N)cc1
Reactant: O=C(Cl)c1ccccc1
Product: COc1ccc(-c2[nH]nc(C)c2NC(=O)c2ccccc2)cc1

Procedure:
The preparation took place in analogy with Example 15a), starting with 500 mg of 5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-ylamine (50) and 315 μl of benzoyl chloride. The following was obtained: 51