Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH2:19][CH2:20]Br)[CH:15]=[CH:14][C:13]=2[C:22]([C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][CH2:32]Br)=[CH:26][C:25]=2[CH:34]2[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:36][CH2:35]2)=[O:23])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:45][O-:46].[Na+].[CH3:48][OH:49]>CO>[CH2:1]([CH:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH2:19][CH2:20][O:46][CH3:45])[CH:15]=[CH:14][C:13]=2[C:22]([C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][CH2:32][O:49][CH3:48])=[CH:26][C:25]=2[CH:34]2[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:36][CH2:35]2)=[O:23])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CO
Reactant: CCCCCC1CCC(c2cc(CCCBr)ccc2C(=O)c2ccc(CCCBr)cc2C2CCC(CCCCC)CC2)CC1
Reactant: C[O-]
Agent: [Na+]
Product: CCCCCC1CCC(c2cc(CCCOC)ccc2C(=O)c2ccc(CCCOC)cc2C2CCC(CCCCC)CC2)CC1
Reaction time: 6 h

Procedure:
In another flask were placed 40 g of 4-pentylcyclohexyl-p-(3-bromopropyl)phenyl ketone and 200 ml of CH3OH and stirred. Thereafter, a sodium methylate-methanol solution prepared by dissolving 3.5 g of Na in 80 ml of absolute CH3OH was added thereto dropwise, and the resulting solution was refluxed. After 6 hours, the reaction solution was concentrated and then poured into water, after which the separated oil layer was extracted with benzene. After the benzene was distilled off, the residue was distilled under reduced pressure to obtain 4-pentylcyclohexyl-p-(3-methoxypropyl)phenyl ketone. The boiling point of this compound was 168°-171° C./0.08 mmHg.
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[N:7]([C@:9]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)([CH2:13][CH:14]=[CH2:15])[CH:10]=[N:11][CH3:12])[CH3:8])([CH3:4])([CH3:3])[CH3:2].B.[Na].CC(C)=O.O>CO>[C:1]([O:5][C:6](=[O:24])[N:7]([C@:9]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)([CH2:13][CH:14]=[CH2:15])[CH2:10][NH:11][CH3:12])[CH3:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: C=CC[C@@](C=NC)(c1ccc(Cl)c(Cl)c1)N(C)C(=O)OC(C)(C)C
Agent: B
Agent: [Na]
Solvent: O
Solvent: CO
Solvent: CC(C)=O
Product: C=CC[C@@](CNC)(c1ccc(Cl)c(Cl)c1)N(C)C(=O)OC(C)(C)C
Reaction time: 3 h
Yield: 100.8 %

Procedure:
tert-Butyl[2-(S)-(3,4-dichlorophenyl)-1-methylimino(4-penten-2-yl)]methylcarbamate (314.5 g) was dissolved in methanol (2 L). Under cooling with ice, sodium boron hydride (38.5 g) was added thereto, and the mixture was stirred for 3 hours. Acetone (177 g) was added to the reaction mixture and then stirred for 30 minutes. The reaction mixture was poured into water, and the resultant mixture was extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine and dried over sodium sulfate anhydrate. The solvent was concentrated under reduced pressure, and the residue was dissolved in methanol (2 L). Under cooling with ice, sodium boron hydride (16.0 g) was added thereto, and the mixture was stirred for 30 minutes. Acetone (49.2 g) was added to the reaction mixture, and the resultant mixture was stirred for 30 minutes. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine and dried over sodium sulfate anhydrate. The solvent was concentrated under reduced pressure, to thereby give the title compound (318.8 g). The compound was used in the next step without further purification.
Reaction SMILES: [ClH:1].[NH2:2][C@@H:3]([CH3:10])[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].[P:11](Cl)(Cl)(=[O:19])[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[O:12][P:11](=[N:2][C@@H:3]([CH3:10])[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5])=[O:19]
Reactant: O=P(Cl)(Cl)Oc1ccccc1
Reactant: CC(C)OC(=O)[C@H](C)N
Reactant: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)OC(=O)[C@H](C)N=[P+]([O-])Oc1ccccc1Cl
Temperature: -78 °C
Reaction time: 1 h
Yield: 88.4 %

Procedure:
(S)-isopropyl 2-aminopropanoate hydrochloride (Oakwood, 500 mg, 2.98 mmol) and phenyl phosphorodichloridate (Aldrich, 662 mg, 2.98 mmol) was suspended in anhydrous DCM (25 mL). The reaction was cooled to −78° C. Triethylamine (604 mg, 830 μl, 5.97 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 1 h, then allowed to warmed up to room temperature and stirred for overnight. The solvent was removed, the residue was washed with dry ether. The filtrate was concentrated to give crude (2S)-isopropyl 2-(chloro(phenoxy)phosphorylamino)propanoate as a light yellow oil (0.8 g, 88%) and used without further purification.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:47]=[CH:46][C:18]([CH2:19][CH:20]2[S:24][C:23](=[O:25])[N:22](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:21]2=[O:45])=[CH:17][CH:16]=1.C(O)(=O)C>O>[CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:47]=[CH:46][C:18]([CH2:19][CH:20]2[S:24][C:23](=[O:25])[NH:22][C:21]2=[O:45])=[CH:17][CH:16]=1
Reactant: Cn1c(CCCOc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)nc2cccnc21
Solvent: O
Solvent: CC(=O)O
Product: Cn1c(CCCOc2ccc(CC3SC(=O)NC3=O)cc2)nc2cccnc21

Procedure:
A procedure similar to that described in Example 12 was repeated, except that 240 mg of 5-[4-{3-(3-methylimidazo[5,4-b]pyridin-2-yl)propoxy}benzyl]-3-triphenylmethylthiazolidine-2,4-dione (prepared as described in Preparation 35) and 10 ml of a 3:1 by volume mixture of acetic acid and water were used, to give the title compound as a crude product. This crude product was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of hexane and ethyl acetate in ratios ranging from 1:3 to 0:1 by volume as the eluent, to give 93 mg of the title compound, melting at 185-186° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH:11]([CH3:28])[CH2:12][C:13]2[CH:27]=[CH:26][C:16]3[O:17][C:18]([C:23]([OH:25])=[O:24])([C:20]([OH:22])=[O:21])[O:19][C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:30][Si:31]([CH3:36])([CH3:35])[CH2:32][CH2:33]O.Cl.[K+].[Br-]>C(Cl)(Cl)Cl>[CH3:30][Si:31]([CH3:36])([CH3:35])[CH2:32][CH2:33][O:24][C:23]([C:18]1([C:20]([O:22][CH2:33][CH2:32][Si:31]([CH3:36])([CH3:35])[CH3:30])=[O:21])[O:17][C:16]2[CH:26]=[CH:27][C:13]([CH2:12][CH:11]([NH:10][CH2:9][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[OH:29])[CH3:28])=[CH:14][C:15]=2[O:19]1)=[O:25]
Reactant: C[Si](C)(C)CCO
Reactant: CC(Cc1ccc2c(c1)OC(C(=O)O)(C(=O)O)O2)NCC(O)c1cccc(Cl)c1
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: CC(Cc1ccc2c(c1)OC(C(=O)OCC[Si](C)(C)C)(C(=O)OCC[Si](C)(C)C)O2)NCC(O)c1cccc(Cl)c1

Procedure:
The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 2-trimethylsilylethanol according to the procedure of Example 30 as a white foam (HCl salt); 1H NMR (CDCl3) δ 0.03 (s, 18H), 1.06 (t, J=8.6 Hz, 4H), 1.33 (bs, 3H), 1.90 (bs, 1H), 2.80 (bs, 1H), 3.18 (bs, 2H), 3.48 (bs, 2H), 4.37 (t, J=8.6 Hz, 4 H), 5.45 (bs, 1H), 6.80 (m, 3H), 7.26 (m, 2H), 7.43 (s, 1H), 8.70 (bs, 1H), 10.10 (bs, 1H); IR (KBr): 1763 cm-1 (C=O); MS (ES) m/z 622 (MH+); [α]D25 -23° (c, 1.0, CHCl3). Anal. Calcd. for C30H44ClNO7Si2 ·HCl: C, 54.70; H, 6.88; N, 2.13; Cl, 10.76; Si, 8.53. Found: C, 53.96; H, 7.05; N, 1.86; Cl, 8.84; Si, 10.33.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:20][CH2:21][C:22]1[N:23]=[N:24][N:25]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=2)[N:26]=1>C1(C)C=CC=CC=1>[BrH:20].[Cl:33][C:29]1[CH:28]=[C:27]([N:25]2[N:24]=[N:23][C:22]([CH2:21][PH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[N:26]2)[CH:32]=[CH:31][CH:30]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Clc1cccc(-n2nnc(CBr)n2)c1
Solvent: Cc1ccccc1
Product: Br
Product: Clc1cccc(-n2nnc(C[PH](c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
Temperature: 80 °C
Yield: 90 %

Procedure:
Triphenylphosphine (89.4 mg, 0.341 mmol) was added to 5-bromomethyl-2-(3-chloro-phenyl)-2H-tetrazole (93.2 mg, 0.341 mmol) in toluene (5 mL). The reaction was heated at 80° C. under Argon for 4.5 hours. The reaction was cooled and concentrated to yield the title compound as a white solid (165.1 mg, 90%). 1H NMR CDCl3 δ (ppm): 7.96 (m, 6H), 7.80 (m, 4H), 7.70 (m, 6H), 7.44 (d, 2H), 7.28 (s, 1H), 6.17 (d, 2H).
Reaction SMILES: [BH4-].[Na+].[O:3]=[C:4]1[CH2:10][CH:9]([CH:11]=[O:12])[C:6]2([CH2:8][CH2:7]2)[NH:5]1>CO.O>[OH:12][CH2:11][CH:9]1[C:6]2([CH2:8][CH2:7]2)[NH:5][C:4](=[O:3])[CH2:10]1
Reactant: O=CC1CC(=O)NC12CC2
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C1CC(CO)C2(CC2)N1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium borohydride (1.4 g, 6.6 mmol) was added to a stirred solution of 5-oxo-4-azaspiro[2.4]heptane-7-carbaldehyde (0.51 g, 3.3 mmol) in methanol (8 mL) and water (12 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was dried over sodium sulfate and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by silica gel chromatography (1:10 methanol in dichloromethane, Rf=0.4) to give 7-(hydroxymethyl)-4-azaspiro[2.4]heptan-5-one. 1H NMR (400 MHz, CD3OD) δ 3.65-3.42 (m, 2H), 2.73-2.55 (m, 1H), 2.46-2.22 (m, 2H), 1.11-0.92 (m, 1H), 0.83-0.59 (m, 3H).
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]2[S:26][C:27]([C:29]([OH:31])=O)=[CH:28][C:22]=2[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.Cl.[N:34]1[CH:39]=[CH:38][C:37]([N:40]2[CH2:45][CH2:44][C:43]3([CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)[CH2:42][CH2:41]2)=[CH:36][CH:35]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[N:34]1[CH:35]=[CH:36][C:37]([N:40]2[CH2:45][CH2:44][C:43]3([CH2:46][CH2:47][N:48]([C:29]([C:27]4[S:26][C:23]5[CH2:24][CH2:25][N:20]([C:18]([O:17][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:19])[CH2:21][C:22]=5[CH:28]=4)=[O:31])[CH2:49][CH2:50]3)[CH2:42][CH2:41]2)=[CH:38][CH:39]=1
Reactant: c1cc(N2CCC3(CCNCC3)CC2)ccn1
Reactant: CC(C)(C)OC(=O)N1CCc2sc(C(=O)O)cc2C1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCc2sc(C(=O)N3CCC4(CC3)CCN(c3ccncc3)CC4)cc2C1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
1,1′-Carbonyldiimidazole (119 mg, 0.741 mmol) and 5-(tert-butoxycarbonyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylic acid (200 mg, 0.706 mmol) were dissolved in dichloromethane (5 ml) and N,N-dimethylformamide (3 ml) and stirred for 1 h at room temperature. 3-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecane dihydrochloride (322 mg, 1.059 mmol), dissolved in a mixture of dichloromethane (5 ml) and triethylamine (0.293 ml, 2.118 mmol), was then added dropwise and the reaction mixture was stirred for 3 days at room temperature. The mixture was diluted with dichloromethane (50 ml) and washed with saturated sodium hydrogen carbonate solution (3×10 ml) and with saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol, 5:1). Yield: 280 mg (80%)
Reaction SMILES: [CH2:1]([N:14]1[C:23](=[O:24])[C:22]2[N:21]([CH3:25])[CH:20]=[N:19][C:18]=2[N:17]([CH3:26])[C:15]1=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH2:13].C[N+]1([O-])CC[O:31]CC1.[OH2:35].S([O-])([O-])=O.[Na+].[Na+]>CC(C)=O.O>[OH:35][CH:12]([CH2:13][OH:31])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][N:14]1[C:23](=[O:24])[C:22]2[N:21]([CH3:25])[CH:20]=[N:19][C:18]=2[N:17]([CH3:26])[C:15]1=[O:16]
Reactant: O
Reactant: C=CCCCCCCCCCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Reactant: C[N+]1([O-])CCOCC1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: Cn1cnc2c1c(=O)n(CCCCCCCCCCCC(O)CO)c(=O)n2C
Reaction time: 1 h
Yield: 82 %

Procedure:
A solution of 1-(12-Tridecenyl)-3,7-dimethylxanthine (1.39 g, 3.86 mmol), 4-methylmorpholine-N-oxide (1.36 g, 11.6 mmol) and potassium osmate dihydrate (14 mg, 0.040 mmol) in acetone/water 1:2 (25 mL) was stirred for 16 hours. Water (25 mL) and sodium sulfite (2 g) were added and the reaction mixture stirred for 1 hour. The reaction mixture was extracted with dichloromethane (3×50 mL), dried using magnesium sulfate and the solvent evaporated to yield 1.25 g (82%) of 1-(12,13-dihydroxytridecyl)-3,7-dimethylxanthine (inventive compound no. 2556) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[CH3:11].[CH:12](I)([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH:12]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[CH3:11])([CH3:14])[CH3:13]
Reactant: CC(=O)c1ccc(O)c(C)c1
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)c1ccc(OC(C)C)c(C)c1
Yield: 74.2 %

Procedure:
A mixture of 1-(4-hydroxy-3-methyl-phenyl)-ethanone 10 g, isopropyl iodide 13.6 g, potassium carbonate 18.4 g and acetone 250 ml was stirred with heating under reflux for twelve hours. The reaction mixture was filtered and the resulting filtrate was concentrated under reduced pressure, and the resulting residue was subjected to a silica gel column chromatography to give 1-(4-isopropoxy-3-methyl-phenyl)-ethanone 9.5 g.
Reaction SMILES: [I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[CH3:10][O:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>ClCCl.C(O)C>[I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:15]2[CH2:16][CH2:17][CH:12]([O:11][CH3:10])[CH2:13][CH2:14]2)=[CH:4][CH:3]=1
Reactant: COC1CCNCC1
Reactant: BrCc1ccc(I)cc1
Solvent: ClCCl
Solvent: CCO
Product: COC1CCN(Cc2ccc(I)cc2)CC1

Procedure:
Prepared analogously to Example 1.1.c. from 4-iodobenzyl bromide and 4-methoxypiperidine. Yield: 0.93 g (66.7% of theory); C13H18INO (M=331.19); calc.: molecular ion peak (M+H)+: 332; found: molecular ion peak (M+H)+: 332; Rf value: 0.55 (silica gel, dichloromethane/ethanol (20:1)).
Reaction SMILES: [C:1]1(=[C:8]([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([O:19]C(C)(C)C)=[O:18])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]1(=[C:8]([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([OH:19])=[O:18])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)/C=C/c1ccc(C(=C2CCCCCC2)c2ccc(O)cc2)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)/C=C/c1ccc(C(=C2CCCCCC2)c2ccc(O)cc2)cc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 57.9 %

Procedure:
To an ice-water cooled mixture of 1,1-dimethylethyl (2E)-3-{4-[cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoate (10) (4.42 g, 10.9 mmol) and CH2Cl2 (20 mL) was slowly added trifluoroacetic acid (10 mL) with stirring under a nitrogen atmosphere. After 3 h, the reaction mixture was filtered. The filtered solid was washed with CH2Cl2 and dried to give 2.2 g of compound 11 as a white solid. The filtrate was concentrated and the impure product was partially purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 9:1) to give a yellow solid. The solid was triturated with Et2O and the suspension was filtered. The filtered solid was dried to give a second crop of compound 11 (354 mg) as a pale tan solid. The Et2O filtrate noted above was concentrated in vacuo and the impure product was crystallized from hexanes and EtOAc. The solid was dried to give a third crop of compound 11 (185 mg) as a pale tan solid. The total yield of 11 was 2.74 g (72%). Analytical data for all three batches were comparable. The analytical data is herein presented for the first batch. 1H NMR (400 MHz, DMSO-d6): δ 1.50 (m, 8H), 2.21 (m, 4H), 6.43 (d, J=15.9 Hz, 1H), 6.65 (d, J=8.4 Hz, 2H), 6.90 (d, J=8.5 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 7.52 (d, J=16.1 Hz, 1H), 7.57 (d, J=8.0 Hz, 2H), 9.28 (s, 1H), 12.21 (br s, 1H). LRMS (ESI): m/z 347 (M−H)−. Anal. Calcd for C23H24O3: C, 79.28; H, 6.94. Found: C, 79.16; H, 6.97.
Reaction SMILES: [C:1]1([C:7]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:15]3=[CH:16][C:17]4[NH:18][C:19]5[C:24]([C:25]=4[CH:26]=[C:14]3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:36]1[N:41]=[C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:39]=[C:38]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[N:37]=1>CN(C)C=O>[C:48]1([C:38]2[N:39]=[C:40]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[N:41]=[C:36]([N:18]3[C:17]4[CH:16]=[C:15]5[C:7]([C:27]6[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=6)([C:1]6[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=6)[C:8]6[C:13]([C:14]5=[CH:26][C:25]=4[C:24]4[C:19]3=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:12][CH:11]=[CH:10][CH:9]=6)[N:37]=2)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: Clc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Reactant: c1ccc(C2(c3ccccc3)c3ccccc3-c3cc4c(cc32)[nH]c2ccccc24)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(-c2nc(-c3ccccc3)nc(-n3c4ccccc4c4cc5c(cc43)C(c3ccccc3)(c3ccccc3)c3ccccc3-5)n2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6 g (14.6 mmol) of 12,12-diphenyl-10,12-dihydro-10-azaindeno[2,1-b]fluorene are dissolved in 100 ml of dimethylformamide under a protective-gas atmosphere, and 0.76 g of NaH, 60% in mineral oil (19 mmol), is added. After 1 hour at room temperature, a solution of 2-chloro-4,6-diphenyl-1,3,5-triazine (4.3 g, 16 mmol) in 50 ml of dimethylformamide is added dropwise. The reaction mixture is then stirred at room temperature for 12 h. After this time, the reaction mixture is poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene. The yield is 8.1 g (12.7 mmol, 87%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N:11]1[CH2:16][CH2:15][O:14][CH2:13][C:12]1=[O:17])[C:5]([OH:7])=O.[Cl:18][C:19]1[CH:35]=[CH:34][C:22]2[NH:23][C:24]([CH:26]([NH2:33])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:25][C:21]=2[CH:20]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1>[Cl:18][C:19]1[CH:35]=[CH:34][C:22]2[NH:23][C:24]([CH:26]([NH:33][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][C:10]([N:11]4[CH2:16][CH2:15][O:14][CH2:13][C:12]4=[O:17])=[C:2]([CH3:1])[CH:3]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:25][C:21]=2[CH:20]=1
Reactant: Cc1cc(C(=O)O)ccc1N1CCOCC1=O
Reactant: NC(c1ccccc1)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)NC(c2ccccc2)c2nc3cc(Cl)ccc3[nH]2)ccc1N1CCOCC1=O

Procedure:
Prepared analogously to Example 1f from 3-methyl-4-(morpholin-3-on-4-yl)benzoic acid, 1-(5-chloro-1H-benzimidazol-2-yl)-1-phenyl-methylamine, TBTU and DIPEA in THF.
Reaction SMILES: Cl.[CH2:2]([N:9]1[CH:13]=[C:12]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24](=[NH:26])[NH2:25])=[CH:20][CH:19]=2)=[O:15])[CH:11]=[N:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:34]([O:36][CH3:37])=[O:35]>O.O1CCCC1>[NH2:26]/[C:24](=[N:25]\[C:34](=[O:35])[O:36][CH3:37])/[C:21]1[CH:20]=[CH:19][C:18]([CH2:17][NH:16][C:14]([C:12]2[CH:11]=[N:10][N:9]([CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:13]=2)=[O:15])=[CH:23][CH:22]=1
Reactant: N=C(N)c1ccc(CNC(=O)c2cnn(Cc3ccccc3)c2)cc1
Reactant: COC(=O)Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)/N=C(\N)c1ccc(CNC(=O)c2cnn(Cc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
57 mg of 1-benzyl-N-[(4-carbamimidoylphenyl)methyl]pyrazole-4-carboxamide hydrochloride and 59 mg of potassium carbonate were dissolved in 0.72 ml of water and 3.6 ml of tetrahydrofuran. The mixture was stirred at room temperature, and 0.012 ml of methyl chloroformate (Sigma-Aldrich) added. Stirring is continued for 1 h, following which the organic layer is removed, and dried in vacuo to obtain the synthetic target. The mass of the compound was verified using LC/MS/MS.
Reaction SMILES: [CH:1]([C:3]1[N:4]=[CH:5][S:6][CH:7]=1)=O.[F-].[K+].[N+:10]([CH3:13])([O-:12])=[O:11].[CH:14](O)(C)C>>[N+:10]([C:13]([CH3:14])=[CH:1][C:3]1[N:4]=[CH:5][S:6][CH:7]=1)([O-:12])=[O:11]
Reactant: CC(C)O
Reactant: O=Cc1cscn1
Reactant: C[N+](=O)[O-]
Agent: [F-]
Agent: [K+]
Product: CC(=Cc1cscn1)[N+](=O)[O-]
Temperature: 62.5 °C
Reaction time: 2 h

Procedure:
In isopropyl alcohol (100 ml) was dissolved 4-formylthiazole (10.9 g), followed by the addition of potassium fluoride (280 mg) and nitromethane (14.46 g). The resulting mixture was stirred at 60 to 65° C. for 2 hours. The reaction mixture was then stirred overnight at room temperature. The solvent was distilled off under reduced pressure. The residue was dissolved in benzene (50 ml), followed by the addition of acetic anhydride (12.29 g) and 4-(dimethylamino)pyridine (588 g). The resulting mixture was heated under reflux for 2 hours. The solvent was distilled off under reduced pressure. Methylene chloride was added to the residue. The resulting mixture was washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was then dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (hexane : ethyl acetate=1:1), whereby the title compound (8.73 g) was obtained as vividly yellow crystals.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)[CH2:6][CH2:5]1.[CH2:19]([Br:21])[CH3:20].O>CN(C)C=O>[BrH:21].[CH2:19]([N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH:7]2[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]2)=[N:11]1)[CH3:20]
Reactant: CN1CCC(c2n[nH]c3ccccc23)CC1
Reactant: CCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Br
Product: CCn1nc(C2CCN(C)CC2)c2ccccc21
Temperature: 25 °C
Yield: 52.8 %

Procedure:
To a stirred suspension of 0.86 g of sodium hydride (50% oil dispersion) in 50 ml of dimethylformamide was added, dropwise, 3.0 g of 3-(1-methyl-4-piperidinyl)-1H-indazole in 15 ml of hot dimethylformamide. The reaction mixture was stirred at ambient temperature and 1.34 ml of ethyl bromide in 10 ml of dimethylformamide was added, dropwise. The reaction was stirred overnight at ambient temperature and poured into water. The aqueous suspension was extracted with ethyl acetate (2X, 100 ml). The extracts were combined, washed with water, dried over anhydrous magnesium sulfate, and the solvent evaporated in vacuo to yield an oil. The oil was dissolved in a minimum amount of ethanol-ether, and a saturated solution of ether-hydrogen bromide was added. The salt was recrystallized from ethanol-ether to yield 2.4 g (52.8%) of product, mp 240°-242° C.
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:7]=[CH:6][S:5][CH:4]=1.[C:8]1([P:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1C=CC=CC=1>[Br-:1].[CH:4]1[S:5][CH:6]=[CH:7][C:3]=1[CH2:2][P+:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: BrCc1ccsc1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: [Br-]
Product: c1ccc([P+](Cc2ccsc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C

Procedure:
34.3 G. of 3-bromomethyl-thiophene and 61.0 g. of triphenylphosphine were dissolved in 500 ml. of benzene. The resulting mixture was refluxed overnight under argon and then cooled to room temperature. The tan phosphonium salt which precipitated was collected by filtration, washed several times with toluene and dried at 100° C. under high vacuum to yield (3-thenyl)triphenylphosphonium bromide, m.p. >270° C.