Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O.[C:34]([O:37][CH2:38][C:39]1[NH:40][CH:41]=[C:42]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=2)[C:43](=[O:45])[CH:44]=1)(=[O:36])[CH3:35].[CH2:56](O)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>O1CCCC1>[C:34]([O:37][CH2:38][C:39]1[CH:44]=[C:43]([O:45][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C:42]([O:46][CH2:47][C:48]2[CH:49]=[CH:50][C:51]([O:54][CH3:55])=[CH:52][CH:53]=2)=[CH:41][N:40]=1)(=[O:36])[CH3:35]
Reactant: OCc1ccccc1
Reactant: COc1ccc(COc2c[nH]c(COC(C)=O)cc2=O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc(COc2cnc(COC(C)=O)cc2OCc2ccccc2)cc1
Reaction time: 8 h
Yield: 60.8 %

Procedure:
A solution of triphenylphosphine (39.3 g, 150 mmol) in tetrahydrofuran (600 ml) was treated at 0° C. with bis(1-methylethyl) (E)-1,2-diazenedicarboxylate (30 ml, 152 mmol). After 10 minutes [5-({[4-(methoxy)phenyl]methyl}oxy)-4-oxo-1,4-dihydro-2-pyridinyl]methyl acetate (33.5 g, 110 mmol) (for a synthesis, see WO2004058144, Example 60(c)) was added. After 10 minutes benzyl alcohol (12.4 ml, 120 mmol) was added and the mixture was stirred overnight. Evaporation and chromatography on silica eluting with 20-50% ethyl acetate in hexane afforded an oil (26.3 g, 61%).
Reaction SMILES: [CH3:1][S:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[CH:15]=[C:14]([NH2:16])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:17]1([C:23]2[O:27][CH:26]=[N:25][C:24]=2[C:28](O)=[O:29])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH3:1][S:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:28]([C:24]3[N:25]=[CH:26][O:27][C:23]=3[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:29])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(Cn2cc(N)cn2)o1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Product: CS(=O)(=O)c1ccc(Cn2cc(NC(=O)c3ncoc3-c3ccccc3)cn2)o1

Procedure:
Following general procedure B followed by C, starting from 1-(5-methanesulfonyl-furan-2-ylmethyl)-1H-pyrazol-4-ylamine and 5-phenyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=0.94 min; [M+H]+=413.29.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:8])=[CH:5][CH:4]=1.[O:17]1CCOCC1>>[O:17]=[C:9]([C:7]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:16][CH:15]=1)=[O:8])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: C1COCCO1
Reactant: CCOC(=O)CC(=O)c1ccc(OC)cc1
Product: CCOC(=O)C(=O)C(=O)c1ccc(OC)cc1
Temperature: 25 °C

Procedure:
A suspension of ethyl p-methoxybenzoylacetate (16.3 mL, 85 m mol) and SeO2 (9.9 g, 89 m mol) in 80 mL of dioxane was heated to reflux overnight. After being cooled down to rt, the reaction mixture was filtered to remove inorganic solid. The filtrate was concentrated under reduced pressure and treated with benzene. The benzene solution was concentrated to dryness under reduced pressure to yield ethyl 2,3-dioxo-(p-methoxyphenyl) -propionate, which was used in next step without further purification.
Reaction SMILES: [CH:1]1([NH:4][C:5](=[O:30])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[C:19](=[O:23])[N:18]([CH2:24][CH:25]3[CH2:27][CH2:26]3)[CH:17]=[C:16]4[CH:28]=O)[CH:7]=2)[CH2:3][CH2:2]1.[N:31]1([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>>[N:31]1([CH:37]2[CH2:42][CH2:41][N:40]([CH2:28][C:16]3[C:15]4[C:20](=[CH:21][CH:22]=[C:13]([C:8]5[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=5[CH3:12])[C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)=[O:30])[CH:14]=4)[C:19](=[O:23])[N:18]([CH2:24][CH:25]4[CH2:27][CH2:26]4)[CH:17]=3)[CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc2c(=O)n(CC3CC3)cc(C=O)c2c1
Reactant: C1CCN(C2CCNCC2)CC1
Product: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc2c(=O)n(CC3CC3)cc(CN3CCC(N4CCCCC4)CC3)c2c1

Procedure:
The title compound was prepared as a solid by the method of Example 59 step iv) using product of Example 59 step iii) and 1,4′-bipiperidine.
Reaction SMILES: C(O)[C@H]1O[C@H](O[C@:9]2([CH2:18]O)[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11](O)[C@@H:10]2O)[C@H](O)[C@@H](O)[C@@H]1O.[CH2:24](O)[C:25]([NH2:30])(CO)CO>>[NH2:30][CH2:25][CH2:24][C:10]1[CH:9]=[CH:18][C:14]([OH:15])=[C:12]([OH:13])[CH:11]=1
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Reactant: NC(CO)(CO)CO
Product: NCCc1ccc(O)c(O)c1
Reaction time: 1.33 h

Procedure:
The pooled supernatant was underlayed with 16 mL of a 36 % sucrose solution prepared in 10 mM Tris (pH 9.0). The supernatant was then ultracentrifuged at 18,000 rpm in a Beckman SW28 rotor for 80 min at 4° C. to pellet recombinant virus. After ultracentrifugation, the supernatant was removed from the visible virus pellet by aspiration, and the pellet resuspended in 1.0-1.5 mL 10 mm Tris (pH 9.0). This suspension was dounced about 7 times on ice to provide a suspension having a milky, even consistency. The recombinant virus suspension was then transferred in 20-40μL aliquots to 2 mL plastic screw-capped FALCON tubes, titred and stored at -70° C. Typical virus stocks prepared in this way were found to have viral titres of about 1010 pfu/mL.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[O:15][CH:14]([CH2:17]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:13][C:12]=3[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:35][NH2:36]>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[O:15][CH:14]([CH2:17][NH:36][CH3:35])[CH2:13][C:12]=3[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(-c4ccccc4)cc(-c4cccc(F)c4)c3O2)cc1
Product: CNCC1Cc2cc(-c3ccccc3)cc(-c3cccc(F)c3)c2O1

Procedure:
The title compound was prepared (0.058 g, 74%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-fluorophenyl)-5-phenyl-2,3-dihydro-1-benzofuran-2-yl]methyl}4-methylbenzenesulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH:19]([CH3:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:19]([CH3:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(C)Br
Reactant: Oc1ccc(OCc2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CC(C)Oc1ccc(OCc2ccccc2)cc1

Procedure:
A solution of 4-benzyloxyphenol (4.2 g) in dimethyl formamide (50 ml) was treated with sodium hydride (840 mg) of a 60% dispersion), and the mixture stirred until evolution of gas ceased. There was then added ethyl 3-bromobutyrate (2.9 ml), and the solution stirred overnight. It was then poured into water (300 ml) and the mixture extracted with ether (3×50 ml). The combined extracts were washed with water (3×) and brine, dried (MgSO4) and evaporated to give a crude product as a brown oil (6 g). This was purified by chromatography on silica, eluting with hexane containing increasing amounts of ethyl acetate to give ethyl 3-(4-benzyloxyphenoxy)butyrate as a colourless crystalline solid (4.5 g) NMR (d6DMSO) δ 1.25(3H,t); 1.8-2.0(2H,m); 2.45(2H,t); 3.9(2H,t); 4.1(2H,q); 5.0(2H,s); 6.8-7.0(4H,m); 7.4(5H,m); m/e 314 (M+H)+.
Reaction SMILES: CN([CH:4]=[O:5])C.O=P(Cl)(Cl)Cl.[N:11]1[CH:12]=[CH:13][N:14]2[CH:19]=[C:18]([CH2:20][C:21]3[N:25]4[N:26]=[C:27]([C:30]5[CH:31]=[N:32][N:33]([CH3:35])[CH:34]=5)[CH:28]=[CH:29][C:24]4=[N:23][CH:22]=3)[CH:17]=[CH:16][C:15]=12>O>[CH3:35][N:33]1[CH:34]=[C:30]([C:27]2[CH:28]=[CH:29][C:24]3[N:25]([C:21]([CH2:20][C:18]4[CH:17]=[CH:16][C:15]5[N:14]([C:13]([CH:4]=[O:5])=[CH:12][N:11]=5)[CH:19]=4)=[CH:22][N:23]=3)[N:26]=2)[CH:31]=[N:32]1
Reactant: CN(C)C=O
Reactant: Cn1cc(-c2ccc3ncc(Cc4ccc5nccn5c4)n3n2)cn1
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: Cn1cc(-c2ccc3ncc(Cc4ccc5ncc(C=O)n5c4)n3n2)cn1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
DMF (2 mL) was cooled down to 0° C. and then POCl3 (0.130 mL, 1.397 mmol) was added slowly. The solution was stirred for 10 min then it was warmed up to rt and the 3-(imidazo[1,2-a]pyridin-6-ylmethyl)-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazine (Example 10, 200 mg, 0.607 mmol) was introduced. The RM was warmed up to 120° C. and stirred for 2 h. It was cooled down to rt and water was added. It was extracted twice with EtOAc. Combined organic layers was washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM) to afford after evaporation of the solvent the title compound as a yellow solid (tR 0.7 min (conditions 2), MH+=358).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30]([OH:32])=O)[C:25]=1[CH3:33])(=[O:12])=[O:11].[N:34]1([CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH2:38][CH2:37][CH2:36][CH2:35]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30]([N:42]2[CH2:43][CH2:44][CH:39]([N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)[CH2:40][CH2:41]2)=[O:32])[C:25]=1[CH3:33])(=[O:12])=[O:11]
Reactant: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4cccc(Cl)c4Cl)cc32)c(C)c1C(=O)O
Reactant: C1CCN(C2CCNCC2)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4cccc(Cl)c4Cl)cc32)c(C)c1C(=O)N1CCC(N2CCCC2)CC1

Procedure:
5-[5-(2,3-Dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 mg, 0.2 mmol) was coupled with 4-pyrrolidin-1-yl-piperidine (31 mg, 1.2 eq.) using HOBt (1.2 eq.), EDAC.HCl (1.2 eq.) and TEA (3 eq.) in DMF at rt for overnight to give the titled compound. MS m/z 639 [M−1].
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:18]=[CH:17][NH:16][N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>N1C=CC=CC=1.O>[CH3:19][S:20]([N:16]1[CH:17]=[CH:18][C:14]([C:11]2[CH:12]=[CH:13][C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:9][CH:10]=2)=[N:15]1)(=[O:22])=[O:21]
Reactant: CS(=O)(=O)Cl
Reactant: c1ccc(Oc2ccc(-c3cc[nH]n3)cc2)cc1
Solvent: c1ccncc1
Solvent: O
Product: CS(=O)(=O)n1ccc(-c2ccc(Oc3ccccc3)cc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.4 %

Procedure:
To a solution of 3-(4-phenoxyphenyl)-1H-pyrazole (125 mg, 0.529 mmol) in pyridine (10 mL) at room temperature was added neat methanesulfonyl chloride (50 μL, 0.64 mmol). After stirring overnight at room temperature, the reaction was diluted with water. Column chromatography afforded 152 mg (91%) of the title compound as white solid, mp 136° C. 1H NMR (CDCl3): δ 8.06 (d, J=3.0 Hz, 1H), 7.84 (d, J=8.7 Hz, 2H), 7.37 (t, J=8.7 Hz, 2H), 7.14 (t, J=7.5 Hz, 1H)), 7.06 (d, J=8.7 Hz, 2H), 7.06-7.04 (m, 2H), 6.72 (d, J=3.0 Hz, 1H), 3.38 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[C:9]3[CH:19]=[C:20]([CH:23]([CH3:25])[CH3:24])[CH:21]=[CH:22][C:8]=3[S:7][C:6]=2[CH:26]=1.[OH:27][CH2:28][CH2:29]CN1CCNCC1.C(Cl)(Cl)Cl>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH:10]([N:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH2:29][CH2:28][OH:27])[CH2:16][CH2:17]3)[C:9]3[CH:19]=[C:20]([CH:23]([CH3:24])[CH3:25])[CH:21]=[CH:22][C:8]=3[S:7][C:6]=2[CH:26]=1
Reactant: OCCCN1CCNCC1
Reactant: CC(C)c1ccc2c(c1)C(N1CCN(C)CC1)Cc1ccc(F)cc1S2
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: CC(C)c1ccc2c(c1)C(N1CCN(CCCO)CC1)Cc1ccc(F)cc1S2

Procedure:
A mixture of 4.0 g 10-chloro-3-fluoro-8-isopropyl-10,11-dihydrodibenzo (b,f) thiepin (Example 1), 4.0 g 1-(3-hydroxypropyl) piperazine (T. Zawisa et al., Acta Polon. Pharm. 22, 477, 1965) and 7 ml of chloroform was refluxed for 5 hours and then processed in the manner described in Example 2. 4.4 g (76%) of an oily base which was converted to a crystalline dimaleate, m.p. 106°-108° C. (ethanol) was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([O:11][CH2:12][CH2:13][CH3:14])[CH:3]=1.[F:15][B-:16]([F:19])([F:18])[F:17].[CH2:20]([O+](CC)CC)[CH3:21]>>[F:15][B-:16]([F:19])([F:18])[F:17].[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](=[NH:8])[O:7][CH2:20][CH3:21])=[C:4]([O:11][CH2:12][CH2:13][CH3:14])[CH:3]=1
Reactant: CCCOc1cc(C)ccc1C(N)=O
Reactant: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Product: CCCOc1cc(C)ccc1C(=N)OCC

Procedure:
reaction of 4-methyl-2-propoxybenzamide (I196 g) with triethyloxonium tetrafluoroborate yielded crude ethyl 4-methyl-2-propoxybenzimidate tetrafluoroborate which on reaction with a saturated solution of ethanolic ammonia and treatment with hydrochloric acid yielded 4-methyl-2-propoxybenzamidine hydrochloride, (8.74 g), m.p. 228°-30° C.;
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[S:11][S:12][C:13]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]([F:27])([F:26])[F:25])=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(O)(=O)C>[OH:8][CH2:9][C:10]1[S:11][S:12][C:13]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]([F:27])([F:26])[F:25])=[CH:14][CH:15]=1
Reactant: CC(C)(C)[Si](C)(C)OCC1=CC=C(COc2ccccc2C(F)(F)F)SS1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: OCC1=CC=C(COc2ccccc2C(F)(F)F)SS1
Reaction time: 7 h
Yield: 58 %

Procedure:
To a stirred solution of the 3-[(tert-butyldimethylsilyloxy)methyl]-6-[(2-trifluoromethylphenyloxy)methyl]-1,2-dithiin obtained above (70 mg, 0.16 mmol) in 2 mL THF was added a mixture of 1.0 mL of 1M tetrabutylammonium fluoride in THF and 0.6 mL of acetic acid. The reation mixture was stirred for 7 h until TLC analysis showed the reaction to be complete, then concentrated in vacuo. The residue was partitioned between 20 mL of water and 20 mL ethyl acetate. The organic phase was washed with 3% solution of aqueous sodium bicarbonate (50 mL), water, dried over sodium sulfate, and then concentrated to a small volume. The residue was purified by silica gel chromatography (ethyl acetate-hexane, 1:3) to yield 30 mg (58%) of the title compound; 1H NMR (CDCl3):δ7.60 (dd, J=8.0, J=l.6, 1 H), 7.50 (t, J=8.4, 1 H), 7.08 (t, J=8.0, 1 H), 6.99 (d, J=8.0 Hz, 1 H), 6.54 (d, J=6.0 Hz, 1 H), 6.44 (d, 1 H, J=6.0), 4.76 (s, 2 H), 4.30 (s, 2 H), 1.93 (bs, 1 H); 13C NMR (CDCl3):161.14, 135.73, 133.26, 128.84, 127.31 (q, J=5.4), 126.59, 125.06, 123.33, 120.90, 113.11, 69.45, 64.59; EI-MS:m/z 320.62.
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[O:18][C:17]3[CH:19]=[C:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[NH2:27][CH2:28][CH2:29][OH:30]>C(#N)C>[CH3:26][S:23]([C:20]1[CH:21]=[CH:22][C:16]2[O:15][CH2:14][CH:13]([CH2:12][NH:27][CH2:28][CH2:29][OH:30])[O:18][C:17]=2[CH:19]=1)(=[O:24])=[O:25]
Reactant: Cc1ccc(S(=O)(=O)OCC2COc3ccc(S(C)(=O)=O)cc3O2)cc1
Reactant: NCCO
Solvent: CC#N
Product: CS(=O)(=O)c1ccc2c(c1)OC(CNCCO)CO2

Procedure:
Preparation according to Example 25 using [7-(methylsulfonyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (0.018 g, 0.046 mmol), 2-aminoethanol (0.5 ml), ACN (3 ml). 1H-NMR (400 MHz, CD3OD): δ 7.47 (1H, d, J 2), δ 7.42 (1H, dd, J 8, 2), δ 7.07 (1H, d, J 8.0), δ 4.43 (1H, dd, J 12, 2.4), δ 4.37 (1H, m)), δ 4.09 (1H, dd J 12, 7.2), δ 3.68 (2H, t, J 5.6), δ 3.07 (3H, s), δ 2.94 (2H, m), 2.80 (2H, m) ppm (J-values are in Hz and shifts relative to solvent-peak at 3.31 ppm).
Reaction SMILES: C[O-].[Na+].CO.[O:6]=[C:7]1[C:15]2[C:10](=[CH:11][C:12]([NH:16][C:17]3[C:18]4[CH2:25][CH2:24][CH2:23][C:19]=4[N:20]=[CH:21][N:22]=3)=[CH:13][CH:14]=2)[CH2:9][CH2:8]1.[CH2:26]([N:33]1[CH2:38][CH2:37][CH:36]([CH:39]=O)[CH2:35][CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[O:6]=[C:7]1[C:15]2[C:10](=[CH:11][C:12]([NH:16][C:17]3[C:18]4[CH2:25][CH2:24][CH2:23][C:19]=4[N:20]=[CH:21][N:22]=3)=[CH:13][CH:14]=2)[CH2:9][C:8]1=[CH:39][CH:36]1[CH2:35][CH2:34][N:33]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:38][CH2:37]1
Reactant: O=C1CCc2cc(Nc3ncnc4c3CCC4)ccc21
Reactant: O=CC1CCN(Cc2ccccc2)CC1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: O=C1C(=CC2CCN(Cc3ccccc3)CC2)Cc2cc(Nc3ncnc4c3CCC4)ccc21
Reaction time: 1.5 h
Yield: 40.6 %

Procedure:
Under ice cooling, 1.70 g of a 28% sodium methoxide·methanol solution was added to 1.96 g of 4-(1-oxoindan-5-yl)amino-5,6-dihydro-7H-cyclopenta[d]pyrimidine dissolved in tetrahydrofuran, and then 1.80 g of 1-benzyl-4-formylpiperidine was added dropwise thereto. After the mixture was stirred for 1.5 hours, a saturated saline solution was added to the reaction mixture, and the mixture was extracted with chloroform. The extract was dried over anhydrous sodium sulfate and condensed under reduced pressure. The obtained residue was applied to silica gel column chromatography and then recrystallized from chloroform to obtain 1.35 g of the title compound as pale yellow crystal.
Reaction SMILES: [CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9](=O)[NH:10][CH:11]=[N:12]2)[CH3:5].[NH2:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH2:30][C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[C:33]#[N:34])[N:25]=[CH:24]2>>[C:33]([C:32]1[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=1[CH2:30][N:26]1[C:27]2[C:23](=[CH:22][C:21]([NH:20][C:9]3[C:8]4[C:13](=[CH:14][CH:15]=[CH:16][C:7]=4[O:6][C@H:4]([CH3:5])[C:3]([N:2]([CH3:19])[CH3:1])=[O:18])[N:12]=[CH:11][N:10]=3)=[CH:29][CH:28]=2)[CH:24]=[N:25]1)#[N:34]
Reactant: N#Cc1ccccc1Cn1ncc2cc(N)ccc21
Reactant: C[C@@H](Oc1cccc2nc[nH]c(=O)c12)C(=O)N(C)C
Product: C[C@@H](Oc1cccc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4C#N)c3)c12)C(=O)N(C)C
Yield: 81 %

Procedure:
Using the same procedure as in Example 18, (2R)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide (220 mg, 0.84 mmol) and 2-[(5-amino-1H-indazol-1-yl)methyl]benzonitrile (1.1 equivalents) were reacted to give the title compound as a beige foam (334 mg, 81%); NMR spectrum (CDCl3) 1.72 (d, 3H), 3.06 (s, 3H), 3.14 (s, 3H), 5.43 (q, 1H), 5.83 (s, 2H), 6.81 (d, 1H), 7.01 (d, 1H), 7.37 (t, 1H), 7.42-7.47 (m, 3H), 7.60 (t, 1H), 7.70 (d, 1H), 7.86 (d, 1H), 8.10 (s, 1H), 8.47 (s, 1H), 8.62 (s, 1H), 10.92 (br s, 1H); Mass spectrum MH+ 492.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[SH:12])=[CH:9][CH:8]=[C:7]([Cl:13])[CH:6]=2.S(OCC)(O[CH2:18][CH3:19])(=O)=O>[OH-].[Na+]>[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[S:12][CH2:18][CH3:19])=[CH:9][CH:8]=[C:7]([Cl:13])[CH:6]=2
Reactant: CCOS(=O)(=O)OCC
Reactant: Nc1cnc2cc(Cl)ccc2c1S
Agent: [Na+]
Agent: [OH-]
Product: CCSc1c(N)cnc2cc(Cl)ccc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 84.6 %

Procedure:
21.06 g (0.1 mole) of 3-amino-7-chloro-4-quinoline-thiol are dissolved in 100 ml of a 2 molar sodium hydroxide solution, whereupon 19.27 g (0.125 mole) of diethyl sulfate are added. The reaction mixture is heated to boiling for 2 hours, cooled to room temperature and extracted with dichloro ethane. The dichloro ethane solution is dried, clarified and evaporated. Thus 20.2 g of 3-amino-4-ethylthio-7-chloro-quinoline are obtained, yield 85%, m.p.: 105°-106° C. (after crystallization from methanol).
Reaction SMILES: [C:1](=[O:8])([O:3][CH2:4][CH2:5][CH2:6][CH3:7])[NH2:2].[CH2:9]=[C:10]([CH3:12])[CH3:11]>C(O)CCC>[C:10]([NH:2][C:1](=[O:8])[O:3][CH2:4][CH2:5][CH2:6][CH3:7])([CH3:12])([CH3:11])[CH3:9]
Reactant: CCCCOC(N)=O
Reactant: C=C(C)C
Solvent: CCCCO
Product: CCCCOC(=O)NC(C)(C)C
Temperature: 70 °C
Reaction time: 5 h
Yield: 86 %

Procedure:
A stirred mixture of 117 g of butyl carbamate, 5 g of butanol, 17 g of ®LEVATIT SPC-118 and 160 g of a mixture comprising 49 percent by weight of isobutene, 41.5 percent by weight of n-butenes and 9.5 percent by weight of butanes was heated to 70° C. in a stirred autoclave, and stirring was continued at this temperature for 5 hours. Thereafter, the catalyst was separated off and the mixture was distilled under reduced pressure. 149 g (86% of theory) of butyl N-tert.-butylcarbamate of boiling point 110°-111° C./20 mbar were obtained. No substantial amount of diisobutene was detected.
Reaction SMILES: C(OC([NH:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:11][CH2:10]1)=O)(C)(C)C.C(N(CC)CC)C.F[C:25]1[C:34]([CH3:35])=[C:33]2[C:28]([C:29](=[O:43])[C:30]([C:40]([OH:42])=[O:41])=[CH:31][N:32]2[C@@H:36]2[CH2:38][C@@H:37]2[F:39])=[CH:27][CH:26]=1>CS(C)=O>[NH2:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][N:14]([C:25]3[C:34]([CH3:35])=[C:33]4[C:28]([C:29](=[O:43])[C:30]([C:40]([OH:42])=[O:41])=[CH:31][N:32]4[C@@H:36]4[CH2:38][C@@H:37]4[F:39])=[CH:27][CH:26]=3)[CH2:13]2)[CH2:10][CH2:11]1
Reactant: CC(C)(C)OC(=O)NC1([C@@H]2CCNC2)CC1
Reactant: Cc1c(F)ccc2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: Cc1c(N2CC[C@@H](C3(N)CC3)C2)ccc2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 427.3 %

Procedure:
After adding 3-(R)-[1-tert-butoxycarbonylaminocyclopropyl]pyrrolidine (185 mg, 817 μmol) and triethylamine (0.50 ml) to dried dimethyl sulfoxide (2 ml), 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (190 mg, 68 μmol) was added thereto and it was heated under reflux for 17 hours under a nitrogen atmosphere. After concentrating the reaction solution under a reduced pressure, the residue was dissolved in chloroform (50 ml). After washing the organic layer with a 10% aqueous citric acid solution (25 ml), the organic layer was dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and after adding dropwise concentrated hydrochloric acid (5 ml) to the residue while cooling with ice, stirring at room temperature was performed for 30 minutes. 1 mol/l Hydrochloric acid (5 ml) was then added to the reaction solution, and after washing the yellow acidic aqueous solution with chloroform (20 ml×3), the pH was adjusted to 12.0 with an aqueous sodium hydroxide solution and the insolubles were removed by filtration. After adjusting the pH of the basic aqueous solution to 7.4 using 1 mol/l hydrochloric acid, extraction with chloroform (100 ml×4) was performed. After drying over anhydrous sodium sulfate, the solvent was evapolated under a reduced pressure. The residue thus obtained was purified by preparative chromatography (development at the lower layer of a 7:3:1 mixture of chloroform:methanol:water), recrystallized in ethanol, and dried under a reduced pressure. 112 mg (43%) of the title compound was thereby obtained in the form of yellow crystals.
Reaction SMILES: C1(C2C=CC=CC=2)C=CC([C:7]([OH:19])([CH2:17]Cl)[CH2:8]C2C=CC(Cl)=CC=2Cl)=CC=1.[H-].[Na+].[NH:28]1[CH:32]=[CH:31][N:30]=[CH:29]1>C(#N)C>[N:28]1([CH2:17][CH:7]([OH:19])[CH3:8])[CH:32]=[CH:31][N:30]=[CH:29]1
Reactant: OC(CCl)(Cc1ccc(Cl)cc1Cl)c1ccc(-c2ccccc2)cc1
Reactant: c1c[nH]cn1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: CC(O)Cn1ccnc1
Temperature: 80 °C

Procedure:
A solution of 39.15 g (0.1 mol) of 2-(4-biphenylyl)-3-chloro-1-(2,4-dichlorophenyl)-propan-2-ol in 300 ml of acetonitrile is added dropwise to a suspension of 3.6 g (0.12 mol) of sodium hydride and 8.2 g (0.12 mol) of imidazole in 200 ml of acetonitrile. After heating to 80° C. for 3 hours, the cooled reaction mixture is filtered and the crystal mass is washed with water and with acetonitrile. 32.5 g (77% of theory) of 2-(4-biphenylyl)-1-(2,4-dichlorophenyl)-3-(imidazol-1-yl-propan-2-ol of melting point 168° C. are obtained.