Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SiH](CC)(CC)CC.B(F)(F)F.CCOCC.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31](O)[C:32]([CH3:43])([O:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:33]([OH:35])=[O:34])=[CH:27][C:26]=1[O:45][CH3:46])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(Cl)Cl>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:32]([CH3:43])([O:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:33]([OH:35])=[O:34])=[CH:27][C:26]=1[O:45][CH3:46])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: COc1cc(C(O)C(C)(Oc2ccccc2)C(=O)O)ccc1OCc1ccccc1
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: COc1cc(CC(C)(Oc2ccccc2)C(=O)O)ccc1OCc1ccccc1
Temperature: -10 °C
Reaction time: 1.5 h

Procedure:
A stirred solution of Et3SiH (8.67 mL, 54.3 mmol) in CH2Cl2 (45 mL) was treated with BF3.Et2O (6.8 mL, 54.3 mmol). 3-(4-Benzyloxy-3-methoxyphenyl)-3-hydroxy-2-methyl-2-phenoxypropionic acid (7.39 g, 18.1 mmol) in CH2Cl2 (90.5 mL) was then added dropwise via addition funnel, maintaining temperature below −7° C. After the addition was complete, the reaction was stirred for 1.5 h at −10° C., then quenched with 1 M NaOH (18.1 mL) and diluted with H2O (12 mL). 1N HCl was used to adjust pH to 4, followed by separation of layers. The aqueous layer was extracted with CH2Cl2 (2×15 mL), and combined organic layers were washed first with 1N HCl (15 mL), then H2O (15 mL), followed by drying over Na2SO4 and concentration to a gummy orange solid (6.86 g, 97%): MS (EI) 410.2 (M +NH4)+, 391.3 (M−H)−.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[C:8]([C:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=1)[N:7]=[C:6]2[C:27](O)=[O:28].Cl.[CH3:31][O:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[CH2:39][NH:38][CH2:37][CH2:36]2>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[C:8]([C:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=1)[N:7]=[C:6]2[C:27]([N:38]1[CH2:37][CH2:36][C:35]2[C:40](=[CH:41][CH:42]=[C:33]([O:32][CH3:31])[CH:34]=2)[CH2:39]1)=[O:28]
Reactant: COc1cc2nc(-c3cc(OC)c(OC)c(OC)c3)nc(C(=O)O)c2cc1OC
Reactant: COc1ccc2c(c1)CCNC2
Agent: Cl
Product: COc1ccc2c(c1)CCN(C(=O)c1nc(-c3cc(OC)c(OC)c(OC)c3)nc3cc(OC)c(OC)cc13)C2
Yield: 32.7 %

Procedure:
Reaction of 6,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)quinazoline-4-carboxylic acid with 6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 117 (32.7% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.89 and 3.05 (2t, 2H), 3.48-4.05 (m, 20H), 4.40 and 4.92 (2s, 2H), 6.65-7.26 (m, 4H), 7.47 and 7.50 (2s, 1H), 7.78 and 7.83 (2s, 2H); MS (ESI) m/z 546 ([M+H]+).
Reaction SMILES: [N:1]([C@@H:4]1[CH2:8][CH2:7][C@@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]1)=[N+]=[N-].[H][H].C(N(CC)CC)C.Cl[C:27]1[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][N:30]=[C:29]([S:38][CH3:39])[N:28]=1>C(O)C.[Pt]=O>[CH2:36]([O:35][C:33]([C:32]1[C:31]([NH:1][C@@H:4]2[CH2:8][CH2:7][C@@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]2)=[N:30][C:29]([S:38][CH3:39])=[N:28][CH:27]=1)=[O:34])[CH3:37]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1CC[C@@H](N=[N+]=[N-])C1
Reactant: [H][H]
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Agent: O=[Pt]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1cnc(SC)nc1N[C@@H]1CC[C@@H](O[Si](C)(C)C(C)(C)C)C1

Procedure:
To a solution of (−)-(1R,3R)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (540 mg, 2.24 mmol) (from Example 27c supra) in ethanol (30 mL) was added platinum oxide (51 mg, 0.22 mmol) (Aldrich) and the mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 25 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To that solution was added triethylamine (620 μL, 450 mg, 4.48 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (520 mg, 2.24 mmol) (Aldrich) and the mixture was stirred at reflux for 1 hour. The reaction mixture was then cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was collected, dried over sodium sulfate and concentrated to a residue that was purified by silica gel column chromatography with a 0–20% ethyl acetate in hexanes gradient to give (+)-(1R,3R)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 710 mg, 77%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][OH:6].[C:7]([C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1)#[N:8].C(N(CC)CC)C>ClCCl>[C:7]([C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][OH:6])=[O:14])=[CH:11][CH:10]=1)#[N:8]
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Reactant: NCCCCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: N#Cc1ccc(C(=O)NCCCCO)cc1
Temperature: 5 °C
Reaction time: 15 h

Procedure:
100 mmol (9.2 ml) of 4-aminobutanol are slowly added, at a temperature of 5° C., to 100 mmol (16.56 g) of 4-cyanobenzoyl chloride in 400 ml of dichloromethane. While maintaining the temperature at 5° C., 100 mmol (13.9 ml) of triethylamine are added. The reaction mixture is stirred for 15 hours at room temperature before being hydrolysed. The organic phase is then decanted off and washed with a 1N hydrochloric acid solution. After evaporating off the solvent, the residue obtained is purified by chromatography on silica gel using a 97/3 dichloromethane/methanol mixture as eluant to yield the expected product.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.S1C(C[CH:16]2[C:21](=[O:22])[O:20][C:19]([CH3:24])([CH3:23])[O:18][C:17]2=[O:25])=CC2C=CC=CC1=2.S1C(CC(C(O)=O)C(O)=O)=CC2C=CC=CC1=2>>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][CH:16]2[C:21](=[O:22])[O:20][C:19]([CH3:24])([CH3:23])[O:18][C:17]2=[O:25])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: CC1(C)OC(=O)C(Cc2cc3ccccc3s2)C(=O)O1
Agent: O=C(O)C(Cc1cc2ccccc2s1)C(=O)O
Product: CC1(C)OC(=O)C(Cc2ccc(F)cc2)C(=O)O1

Procedure:
The title compound was prepared using 4-fluorobenzaldehyde in place of benzo[b]thiophene-2-carbaldehyde using the procedure described for the preparation of 5-(benzo[b]thiophen-2-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 39: step a).
Reaction SMILES: Cl.[C@@H:2]1([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[CH2:3]1.C[Si](C)(C)Cl.[C:23]1([CH2:36][O:37][C:38](Cl)=[O:39])[C:35]2[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[CH:26]=CC=1.N1C=CC=[CH:43][CH:42]=1>>[C:38]([NH:15][C:14]1[CH:16]=[CH:17][N:10]([C@@H:2]2[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[CH2:3]2)[C:11](=[O:12])[N:13]=1)([O:37][CH2:36][CH:23]1[C:35]2[C:34](=[CH:42][CH:43]=[CH:26][CH:27]=2)[C:33]2[C:28]1=[CH:29][CH:30]=[CH:31][CH:32]=2)=[O:39]
Reactant: O=C(Cl)OCc1cccc2c1Cc1ccccc1-2
Reactant: c1ccncc1
Reactant: Nc1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1
Agent: C[Si](C)(C)Cl
Agent: Cl
Product: O=C(Nc1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1)OCC1c2ccccc2-c2ccccc21
Yield: 97 %

Procedure:
In one embodiment, 5′-O-DMTR-N4-FMOC-2′-deoxycytidine was prepared according to the following protocol. 30 g (37.9 mmol) of 2′-deoxycytidine hydrochloride were silylated with trimethylchlorosilane (75 ml) in pyridine (160 ml), followed by treatment with fluorenylmethoxycarbonyl chloride (33 g, 128 mmol). After hydrolysis with H2O (300 ml) and extraction with AcOEt/H2O, the N4-FMOC-2′-deoxycytidine was obtained in a 97% yield (49.5 g) as a colorless powder.
Reaction SMILES: [H-].[Na+].[C:3]([CH2:6][C:7](=[O:9])[CH3:8])(=[O:5])[CH3:4].[CH2:10]([N:14]([CH2:58][CH2:59][CH2:60][CH3:61])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)(O)[CH:22]=[CH:23][CH:24]=[C:25]([C:34]2[CH:39]=[CH:38][C:37]([N:40]([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:41][CH2:42][CH2:43][CH3:44])=[CH:36][CH:35]=2)[C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[CH:17][CH:16]=1)[CH2:11][CH2:12][CH3:13].Cl([O-])(=O)(=O)=O>CN(C)C=O>[CH2:45]([N:40]([CH2:41][CH2:42][CH2:43][CH3:44])[C:37]1[CH:36]=[CH:35][C:34]([C:25]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[CH:24][CH2:23][CH:22]=[C:21]([C:18]2[CH:17]=[CH:16][C:15]([N:14]([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:58][CH2:59][CH2:60][CH3:61])=[CH:20][CH:19]=2)[C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)=[CH:39][CH:38]=1)[CH2:46][CH2:47][CH3:48].[C:3]([CH2:6][C:7](=[O:9])[CH3:8])(=[O:5])[CH3:4]
Reactant: CCCCN(CCCC)c1ccc(C(=CC=CC(O)(c2ccc(OC)cc2)c2ccc(N(CCCC)CCCC)cc2)c2ccc(OC)cc2)cc1
Agent: [H-]
Agent: [Na+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CN(C)C=O
Solvent: CC(=O)CC(C)=O
Product: CCCCN(CCCC)c1ccc(C(=CCC=C(c2ccc(OC)cc2)c2ccc(N(CCCC)CCCC)cc2)c2ccc(OC)cc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 63.7 %

Procedure:
1.2 g of a 60% sodium hydride was dispersed in 200 ml of well-dried N,N-dimethylformamide (DMF) in a 300-ml. Erlenmeyer flask. To this dispersion, 3.00 g of acetylacetone was slowly added at room temperature and the mixture was stirred for 1 hour. To this mixture, 15.71 g of 1,5-bis-(p-di-n-butylaminophenyl)-1,5-bis-(p-methoxyphenyl)-2,4-pentadiene-1-ol-perchlorate prepared in Synthesis Example 2,5 was slowly added. This reaction mixture was stirred at room temperature for 1 hour. Then the reaction mixture was poured into 1 l of ice water. As a result, solids separated from the reaction mixture. The solids were washed with water and dried under reduced pressure. After the completion of drying, the solids were subjected to column chromatography, so that 10.0 g of 1,5-bis-(p-di-n-butylaminophenyl)-1,5-bis-(p-methoxyphenyl)-1,4-pentadiene-3-acetylacetone (Leuco Dye No. 26 ) according to the present invention was obtained in the form of light yellow viscous material. The yield was 63.7%. The characteristics absorption bands in the infrared spectrum of the thus obtained product were as follows:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20]Cl)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[I-].[Li+].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>CN(C=O)C.C(Cl)Cl.CO.N>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: C1COCCN1
Reactant: ClCCCOc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1
Agent: N
Agent: [I-]
Agent: [Li+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CO
Product: Brc1cnc2[nH]c(-c3ccc(OCCCN4CCOCC4)cc3)nc2c1

Procedure:
A solution of 6-bromo-2-[4-(3-chloropropoxy)phenyl]-3H-imidazo[4,5-b]pyridine (50 mg, 0.14 mmol), lithium iodide (20 mg, 0.15 mmol) and morpholine (0.1 ml, 1.15 mmol) in DMF (5 ml) was heated at 100° C. for 6 h. Column chromatography on silica using methylene chloride/methanol/ammonia as eluent afforded the title compound in almost quantitative yield.
Reaction SMILES: Br[C:2]1C=CC(O)=[C:6]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)[CH:7]=1.[NH2:37][C:38]1[S:39]C(C(=O)C)=C(C)[N:42]=1.[OH-].[K+]>C(O)C>[NH2:42][C:38]1[S:39][C:6]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)=[C:7]([CH3:2])[N:37]=1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(Br)ccc4O)ccc3c1)n2C1CCCCC1
Reactant: CC(=O)c1sc(N)nc1C
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: Cc1nc(N)sc1-c1ccc2cc(-c3nc4cc(C(=O)O)ccc4n3C3CCCCC3)ccc2n1
Yield: 9 %

Procedure:
Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-(2-amino-4-methyl-thiazol-5-yl)-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in ethanol (506 μL, 0.64 mmol) to produce the title compound (8 mg, 9% yield). MS: 484.19 (M+H+); HPLC Procedure A, retention time=8.57 min.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[C:5]([O:17][CH3:18])[C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[H-].[Na+].[CH3:21][OH:22]>>[Cl:1][C:2]1[N:11]=[C:10]([O:22][CH3:21])[C:9]2[C:4](=[C:5]([O:17][CH3:18])[C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1
Reactant: CO
Reactant: COc1cc2c(Cl)nc(Cl)nc2c(OC)c1OC
Agent: [H-]
Agent: [Na+]
Product: COc1cc2c(OC)nc(Cl)nc2c(OC)c1OC
Yield: 97 %

Procedure:
5.00 g (17.3 mmol) of 2,4-dichloro-6,7,8-trimethoxyquinazoline was suspended in 100 ml of methanol, followed by the gradual addition of 1.5 g of sodium hydride. The obtained mixture was heated under reflux. After several hours, the reaction mixture was concentrated under a reduced pressure, followed by the addition of water. The crystal thus precipitated was recovered by filtration, washed with water and air-dried to give 4.80 g of the title compound as a pale-pink crystal.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8](=[O:15])OCC(Cl)(Cl)Cl)[CH:2]=1.[O:16]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[C:23]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[CH:24]=[CH:25][CH:26]=2)=[CH:17]1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[O:16]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[C:23]([N:27]3[CH2:32][CH2:31][N:30]([C:8]([NH:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[O:15])[CH2:29][CH2:28]3)[CH:24]=[CH:25][CH:26]=2)=[CH:17]1
Reactant: O=C(Nc1cccnc1)OCC(Cl)(Cl)Cl
Reactant: c1cc(-c2ccoc2)cc(N2CCNCC2)c1
Solvent: O
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1cccnc1)N1CCN(c2cccc(-c3ccoc3)c2)CC1
Yield: 44.8 %

Procedure:
A mixed solution of 2,2,2-trichloroethyl pyridin-3-ylcarbamate (279 mg, 1.04 mmol), 1-[3-(3-furyl)phenyl]piperazine (215 mg, 0.942 mmol) and diisopropylethylamine (0.328 ml, 1.88 mmol) in dimethylsulfoxide (3.0 ml) was stirred at 70° C. for 3 days. Water was poured into the reaction solution, and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduce pressure. The residue was purified by silica gel column chromatography (ethyl acetate), and recrystallized from a mixed solvent of hexane and ethyl acetate to give the titled compound 147 mg (44.7%) as solid product.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:4]([F:10])=[C:5]([NH2:9])[CH:6]=[CH:7][CH:8]=1.N1C=CN=C1.[N:16]1[CH:21]=[CH:20][CH:19]=[N:18][C:17]=1[O:22][C:23]1[CH:24]=[C:25]([C:32](O)=[O:33])[C:26](=[CH:30][CH:31]=1)[C:27](O)=[O:28].O>CN(C=O)C.C(OCC)(=O)C>[NH2:9][C:5]1[C:4]([F:10])=[C:3]([CH:8]=[CH:7][CH:6]=1)[CH2:2][N:1]1[C:32](=[O:33])[C:25]2[C:26](=[CH:30][CH:31]=[C:23]([O:22][C:17]3[N:18]=[CH:19][CH:20]=[CH:21][N:16]=3)[CH:24]=2)[C:27]1=[O:28]
Reactant: NCc1cccc(N)c1F
Reactant: O=C(O)c1ccc(Oc2ncccn2)cc1C(=O)O
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Nc1cccc(CN2C(=O)c3ccc(Oc4ncccn4)cc3C2=O)c1F
Temperature: 150 °C
Reaction time: 0.08 h
Yield: 10.2 %

Procedure:
3-Aminomethyl-2-fluoro-phenylamine (50.8 mg, 0.362 mmol) and imidazole (26.0 mg, 0.382 mmol) were added to a solution of 4-(pyrimidin-2-yloxy)phthalic acid (94.1 mg, 0.362 mmol) in DMF (2.0 mL), and the mixture was stirred in a Microwave at 300 W, 150° C. for 5 minutes. Water was then added to the reaction mixture, extraction was performed with ethyl acetate, and the organic extract was washed with saturated saline. After drying over magnesium sulfate, it was concentrated under reduced pressure to yield a crude product, which was then purified by column chromatography to yield the title compound (13.4 mg, 10%) as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][C@H:9]([NH:12][C:13]([C:15]2([CH2:20][CH:21]([CH:25]3[CH2:30][CH2:29][CH2:28][CH:27]=[CH:26]3)[C:22]([OH:24])=[O:23])[CH2:19][CH2:18][CH2:17][CH2:16]2)=[O:14])[CH2:8][CH2:7]1)=[O:5])[CH3:2]>C(O)C.[Pd]>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:7][CH2:8][C@H:9]([NH:12][C:13]([C:15]2([CH2:20][CH:21]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[C:22]([OH:24])=[O:23])[CH2:16][CH2:17][CH2:18][CH2:19]2)=[O:14])[CH2:10][CH2:11]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H]1CC[C@@H](NC(=O)C2(CC(C(=O)O)C3C=CCCC3)CCCC2)CC1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)[C@H]1CC[C@@H](NC(=O)C2(CC(C(=O)O)C3CCCCC3)CCCC2)CC1

Procedure:
3-{1-[(cis-4-Ethoxycarbonyl-cyclohexyl)carbamoyl]cyclopentyl}-2-(cyclohex-2-enyl)propanoic acid (185 mg, 0.441 mmol) was dissolved in absolute ethanol (50 ml) and hydrogenated at 50 p.s.i. (3.45 bar) over 5% palladium on charcoal (10 mg) as catalyst. The solution was filtered and the solvent evaporated to give the title compound as a colourless gum (180 mg, 97%). Found: C,65.56; H,9.05; N,3.31. C24H39NO5.H2O requires C,65.57; H,9.39; N,3.18%.
Reaction SMILES: [SH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].I[C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[OH:20])[C:14]([OH:16])=[O:15].[OH-].[K+]>O.[Cu]>[OH:5][CH2:4][C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[S:1][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[OH:20])[C:14]([OH:16])=[O:15]
Reactant: O=C(O)c1ccc(O)c(I)c1
Reactant: OCc1ccccc1S
Agent: [Cu]
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1ccc(O)c(Sc2ccccc2CO)c1

Procedure:
A mixture of 25 gm o-mercaptobenzyl alcohol (0.18 mole), 39.6 gm 3-iodo-4-hydroxy benzoic acid (0.15 mole), 11.43 g copper powder (0.18 mole), 70 cc 40% aqueous potassium hydroxide solution (0.5 mole) and 300 cc water was placed under nitrogen atmosphere and stirred under reflux for 18 hours. After cooling the mixture was diluted with 400 cc of water and extracted twice with 100 cc of ethyl acetate to remove neutral products. The aqueous fraction was filtered and the filtrate acidified with conc. HCl to afford the title compound as an oil which solidified and was filtered. There was obtained 32.8 g of solid product.
Reaction SMILES: C([O:3][C:4]([C:6]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[N:7][N:8]=[C:9](Cl)[CH3:10])=O)C.O.[NH2:18][NH2:19]>C(O)(C)C>[NH2:18][N:19]1[C:4](=[O:3])[C:6]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[N:7][N:8]=[C:9]1[CH3:10]
Reactant: CCOC(=O)C(=NN=C(C)Cl)c1cccs1
Reactant: NN
Solvent: O
Solvent: CC(C)O
Product: Cc1nnc(-c2cccs2)c(=O)n1N
Reaction time: 8 h

Procedure:
234 g (0.92 mol) of crude 1-ethoxycarbonyl-4-chloro-4-methyl-1-thien-2-yl-2,3-diazabutadiene were dissolved in 600 ml of isopropanol and 125 g (2.5 mol) of hydrazine hydrate were added at 60° C., whilst stirring. Stirring was continued for 8 hours at 60° C. The reaction solution was concentrated to one-third and water was added. The solid which had precipitated was then filtered off, thoroughly rinsed with water and dried. 125g (65.3% of theory) of 4-amino-3-methyl-6-thien-2-yl-1,2,4-triazin-5-one of melting point 210° C. were obtained.
Reaction SMILES: [C:1]1([CH2:13][C:14]([NH2:16])=[O:15])[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.C[O:18][C:19](=O)[C:20]([C:22]1[C:30]2[C:25](=[CH:26][C:27]([Br:31])=[CH:28][CH:29]=2)[NH:24][CH:23]=1)=O>>[C:1]1([C:13]2[C:14](=[O:15])[NH:16][C:19](=[O:18])[C:20]=2[C:22]2[C:30]3[C:25](=[CH:26][C:27]([Br:31])=[CH:28][CH:29]=3)[NH:24][CH:23]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1
Reactant: COC(=O)C(=O)c1c[nH]c2cc(Br)ccc12
Reactant: NC(=O)Cc1cn2c3c(cccc13)CCC2
Product: O=C1NC(=O)C(c2cn3c4c(cccc24)CCC3)=C1c1c[nH]c2cc(Br)ccc12

Procedure:
Beginning with 2-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)acetamide and (6-Bromo-1H-indol-3-yl)oxoacetic acid methyl ester, the title compound was prepared essentially as described in Example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]3[N:16]([CH3:18])[C:15](=[O:19])[N:14]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[C:13]=3[CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[C:29](OC(=O)C)(=[O:31])[CH3:30]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C:9]2[C:17]3[N:16]([CH3:18])[C:15](=[O:19])[N:14]([CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)[C:13]=3[CH:12]=[CH:11][CH:10]=2)[C:29](=[O:31])[CH3:30])=[CH:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(Cn2c(=O)n(C)c3c(Nc4ccc(Cl)cc4)cccc32)cc1
Solvent: c1ccncc1
Product: COc1ccc(Cn2c(=O)n(C)c3c(N(C(C)=O)c4ccc(Cl)cc4)cccc32)cc1
Temperature: 120 °C

Procedure:
A mixture of 4-[(4-chlorophenyl)amino]-1-(4-methoxybenzyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-one (0.393 g, 1.0 mmol), pyridine (0.1 ml) and acetic anhydride (10 ml) was heated at 120° C. for 4 days. The mixture was evaporated in vacuo. The residue was diluted with ethyl acetate (50 ml), washed with saturated sodium bicarbonate, dried over magnesium sulfate and evaporated in vacuo. The residue was flash chromatographed eluting with 40-50% ethyl acetate/hexanes to give N-(4-chlorophenyl)-N-[1-(4-methoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl]acetamide (0.388 g, quant.) as an oil.
Reaction SMILES: [Na].[N+:2]([NH:5][C:6]([NH2:8])=[NH:7])([O-:4])=[O:3].[CH:9]([CH:11]([CH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)[C:12](OCC)=O)=[O:10]>CO>[N+:2]([NH:5][C:6]1[NH:8][C:9](=[O:10])[C:11]([CH2:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)=[CH:12][N:7]=1)([O-:4])=[O:3]
Reactant: CCOC(=O)C(C=O)Cc1cccnc1
Reactant: N=C(N)N[N+](=O)[O-]
Agent: [Na]
Solvent: CO
Product: O=c1[nH]c(N[N+](=O)[O-])ncc1Cc1cccnc1
Yield: 38 %

Procedure:
Sodium (1.15 g) was dissolved in methanol (50 ml) and nitroguanidine (4.7 g) was added to the cooled solution. The mixture was heated under reflux for 45 minutes, ethyl 2-formyl-3-(3-pyridyl)propionate (9.3 g) was added portionwise and the mixture was heated under reflux for 45 hours and evaporated to dryness. Water was added to the residue and the mixture was extracted with chloroform. The residual aqueous phase was adjusted to pH 5 with acetic acid, and the solid which was precipitated was filtered off, washed and dried to give 2-nitroamino-5-(3-pyridylmethyl)-4-pyrimidone, m.p. 214.5°-216°, in 38% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH3:13])[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([C:27]([OH:29])=[O:28])=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:17][CH:16]=3)[C:6]=2[CH:30]=1.Cl[C:32]1[C:37]2=[N:38][O:39][N:40]=[C:36]2[C:35]([N+:41]([O-:43])=[O:42])=[CH:34][CH:33]=1>N1C=CC=CC=1>[CH2:10]([C:8]1[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[C:22]([C:27]([OH:29])=[O:28])=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:17][CH:16]=2)[C:6]2[CH:30]=[C:2]([NH:1][C:32]3[C:37]4=[N:38][O:39][N:40]=[C:36]4[C:35]([N+:41]([O-:43])=[O:42])=[CH:34][CH:33]=3)[CH:3]=[CH:4][C:5]=2[N:9]=1)[CH2:11][CH2:12][CH3:13]
Reactant: O=[N+]([O-])c1ccc(Cl)c2nonc12
Reactant: CCCCc1nc2ccc(N)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1
Solvent: c1ccncc1
Product: CCCCc1nc2ccc(Nc3ccc([N+](=O)[O-])c4nonc34)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared from 4'-[(6-amino-2-n-butyl-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid and 4-chloro-7-nitro-benzofurazan in pyridine at ambient temperature.
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[CH:5]1.C[O:29][C:30](=O)[CH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]1>>[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][C:30](=[O:29])[CH2:31][C@H:32]5[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]5)[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[CH:5]1
Reactant: COC(=O)C[C@H]1CC[C@H](O)CC1
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4occc34)CC2)CC1
Agent: Cl
Product: O=C(C[C@H]1CC[C@H](O)CC1)N[C@H]1CC[C@H](CCN2CCN(c3nccc4occc34)CC2)CC1

Procedure:
The title compound, white solid (159 mg, quant.), MS (ISP) m/z=469.3 [(M+H)+], was prepared in analogy to example 2 from trans-4-[2-(4-furo[3,2-c]pyridin-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine trihydrochloride (intermediate A) (150 mg, 0.34 mmol) and trans-(4-hydroxy-cyclohexyl)-acetic acid methyl ester [CAS-Nr. 1124174-16-8, WO 2010/031735] (71 mg, 0.41 mmol). The purification was performed by precipitation from Et2O.