Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH2:18])[CH2:4][CH2:3]1.[C:20]([N:28]=[C:29]=[S:30])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(Cl)Cl>[C:20]([NH:28][C:29]([NH:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH3:19])([CH3:1])[CH2:3][CH2:4]1)=[S:30])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC1(C)CCN(c2ccccc2N)c2ccccc21
Reactant: O=C(N=C=S)c1ccccc1
Solvent: ClCCl
Product: CC1(C)CCN(c2ccccc2NC(=S)NC(=O)c2ccccc2)c2ccccc21
Reaction time: 0.07 h

Procedure:
1d (65.4 mg, mmol) and benzoyl isothiocyanate (60 mg) were heated at refluxing CH2Cl2 for 2 h. After cooling, the solvent was evaporated. The resulting crude 1e was dried over vacuum and used directly in the next step: LC-MS ESI, 416.3 (M+H) (10-90% MeOH in H2O with 0.1% TFA in a 4 min run, tR=4.49 min).
Reaction SMILES: C([O:3][C:4](=[O:25])[CH:5]([C:11]1[CH:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[Cl:24])[CH:14]=[CH:15][CH:16]=1)[C:6]([O:8]CC)=[O:7])C.[OH-].[Na+]>>[Cl:24][C:18]1[C:19]([Cl:23])=[CH:20][CH:21]=[CH:22][C:17]=1[C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH:5]([C:4]([OH:25])=[O:3])[C:6]([OH:8])=[O:7])[CH:12]=1
Reactant: CCOC(=O)C(C(=O)OCC)c1cccc(-c2cccc(Cl)c2Cl)c1
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)C(C(=O)O)c1cccc(-c2cccc(Cl)c2Cl)c1
Temperature: 70 °C

Procedure:
2-(2′,3′-Dichloro-[1,1′-biphenyl]-3-yl)propanedioic acid 1,3-diethyl ester (i.e. the product of Step B, 0.30 g, 0.79 mmol) was added to 2% aqueous sodium hydroxide (5 mL), and the reaction mixture was heated at 70° C. for 20 min. The reaction mixture was cooled, quenched with 6 N aqueous hydrochloric acid, and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to yield the title compound (0.20 g).
Reaction SMILES: [CH:1](OCC)=[O:2].[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[O:12][C@@H:13]1[CH2:32][CH2:31][C@@:30]2([CH3:33])[C@@H:15]([CH2:16][CH2:17][C@@H:18]3[C@@H:29]2[C:28](=[O:34])[CH2:27][C@@:26]2([CH3:35])[C@H:19]3[CH2:20][CH2:21][C@@H:22]2[C:23](=[O:25])[CH3:24])[CH2:14]1.[H-].[Na+].CO>CS(C)=O>[CH:1]([CH2:24][C:23](=[O:25])[C@@H:22]1[C@:26]2([CH3:35])[C@H:19]([C@H:18]3[C@H:29]([C:28](=[O:34])[CH2:27]2)[C@:30]2([CH3:33])[C@H:15]([CH2:14][C@H:13]([O:12][CH:7]4[CH2:8][CH2:9][CH2:10][CH2:11][O:6]4)[CH2:32][CH2:31]2)[CH2:16][CH2:17]3)[CH2:20][CH2:21]1)=[O:2]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](OC5CCCCO5)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CO
Product: C[C@]12CC[C@@H](OC3CCCCO3)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)CC=O)[C@@]3(C)CC(=O)[C@@H]12
Reaction time: 4 h

Procedure:
Ethyl formate (0.7 ml) was added to a mixture of 3α-(tetrahydropyran-2ξ-yloxy)-5α-pregnane-11,20-dione (840 mg) and sodium hydride (130 mg) in dry dimethyl sulphoxide (15 ml). The mixture was stirred, under nitrogen for 11/4 hrs., then treated with methyl alcohol to destroy excess sodium hydride, and poured into dilute hydrochloric acid. The precipitate was collected, washed and dried to give title compound (943 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[N:12][C:13]([CH:16]([NH:18][C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[CH3:17])=[CH:14][N:15]=2)=[CH:5][CH:4]=1.N[CH:25]([C:27]1N=NC(NC2C=CC(OC)=CC=2)=NC=1)[CH3:26].C1(C(Cl)=O)CCCCC1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[N:11]=[N:12][C:13]([CH:16]([NH:18][C:19]([CH:21]3[CH2:23][CH2:22][CH2:27][CH2:25][CH2:26]3)=[O:20])[CH3:17])=[CH:14][N:15]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(Nc2ncc(C(C)NC(=O)C3CC3)nn2)cc1
Reactant: COc1ccc(Nc2ncc(C(C)N)nn2)cc1
Agent: O=C(Cl)C1CCCCC1
Product: COc1ccc(Nc2ncc(C(C)NC(=O)C3CCCCC3)nn2)cc1

Procedure:
In a similar manner as described for Intermediate 62, using 6-(1-aminoethyl)-N-[4-(methyloxy)phenyl]-1,2,4-triazin-3-amine (Intermediate 47) (100 mg, 0.41 mmol), and cyclohexanecarbonyl chloride (0.065 mL, 0.45 mmol) to afford N-[1-(3-{[4-(methyloxy)phenyl]amino}-1,2,4-triazin-6-yl)ethyl]cyclohexane-carboxamide (90 mg) as a yellow solid. MS m/z 356 (M+1).
Reaction SMILES: [CH2:1]([O:8][N:9]=[CH:10][C:11]1([C:19]([OH:21])=[O:20])[CH2:16][C@H:15]([CH3:17])[CH2:14][C@H:13]([CH3:18])[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C1C=CC(N=NC2C=CC(S(O)(=O)=O)=CC=2)=CC=1)C.Cl.C([BH3-])#N.[Na+]>CO>[CH2:1]([O:8][NH:9][CH2:10][C:11]1([C:19]([OH:21])=[O:20])[CH2:16][C@H:15]([CH3:17])[CH2:14][C@H:13]([CH3:18])[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[C@@H]1C[C@H](C)CC(C=NOCc2ccccc2)(C(=O)O)C1
Agent: CN(C)c1ccc(N=Nc2ccc(S(=O)(=O)O)cc2)cc1
Agent: Cl
Agent: [BH3-]C#N
Solvent: CO
Product: C[C@@H]1C[C@H](C)CC(CNOCc2ccccc2)(C(=O)O)C1
Temperature: 0 °C

Procedure:
A solution of (3S,5R)-1-(benzyloxyimino-methyl)-3,5-dimethyl-cyclohexanecarboxylic acid (1.8 g, 6.2 mmol) in methanol (120 mL) at 0° C. under a nitrogen atmosphere was added a trace amount of methyl orange. A solution of saturated methanolic HCl was added until a persistent red color was observed. Sodium cyanoborohydride (0.51 g, 8.1 mmol) was added portionwise alternately with methanolic HCl to maintain the red color. The reaction mixture was maintained at 0° C. for an additional 0.5 h and the volatiles were removed in vacuo. The product was used without further purification. MH+292.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH3:37][O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].Cl>FC(F)(F)CO>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:40]3[CH:42]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]
Reactant: COc1cc(N2CCC(CCS(C)(=O)=O)CC2)ccc1N
Reactant: CCOc1ccc(-c2nc3ccccn3c2-c2ccnc(Cl)n2)cc1C(=O)Nc1c(F)cccc1F
Agent: Cl
Solvent: OCC(F)(F)F
Product: CCOc1ccc(-c2nc3ccccn3c2-c2ccnc(Nc3ccc(N4CCC(CCS(C)(=O)=O)CC4)cc3OC)n2)cc1C(=O)Nc1c(F)cccc1F
Temperature: 180 °C
Yield: 44 %

Procedure:
To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.13 g, 0.25 mmol) and 2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (0.077 g, 0.25 mmol) in 2,2,2-trifluoroethanol (1.5 mL) was added HCl (0.13 mL, 4M in dioxane, 0.50 mmol). The reaction was heated at 180° C. for 40 min in the microwave. The reaction mixture was quenched with sodium methoxide (0.5M in MeOH) and concentrated. Purification by flash chromatography, and recrystallization with EtOH provided the title compound (0.082 g, 0.11 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ 1.19-1.30 (m, 2H), 1.39 (t, J=6.6 Hz, 3H), 1.43-1.53 (m, 1H), 1.57-1.68 (m, 2H), 1.74 (d, J=13.9 Hz, 2H), 2.53-2.64 (m, 2H), 2.92 (s, 3H), 3.07-3.18 (m, 2H), 3.66 (d, J=11.4 Hz, 2H), 3.76 (s, 3H), 4.23 (d, J=6.2 Hz, 2H), 6.43-6.53 (m, 2H), 6.63 (s, 1H), 6.86-6.97 (m, 1H), 7.15 (t, J=7.6 Hz, 2H), 7.23 (d, J=8.4 Hz, 1H), 7.32-7.43 (m, 3H), 7.66 (d, J=9.2 Hz, 1H), 7.71 (d, J=11.5 Hz, 1H), 8.01 (s, 1H), 8.16 (d, J=5.5 Hz, 1H), 8.39 (s, 1H), 9.33 (br. s., 1H), 9.71 (s, 1H). MS (ESI) m/z=782 [M+H]+.
Reaction SMILES: [C:1]([C:5]1[C:10]([OH:11])=[CH:9][C:8]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])=[C:7](Br)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:27][N:28]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:5]1[C:10]([OH:11])=[CH:9][C:8]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])=[C:7]([C:27]#[N:28])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1cc(Br)c(NC(=O)c2c[nH]c3ccccc3c2=O)cc1O
Reactant: CN1CCCC1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: CC(C)(C)c1cc(C#N)c(NC(=O)c2c[nH]c3ccccc3c2=O)cc1O
Temperature: 200 °C

Procedure:
To a suspension of N-(4-tert-butyl-2-bromo-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide (C-27-I) (84 mg, 0.2 mmol), Zn(CN)2 (14 mg, 0.12 mmol) in NMP (1 mL) was added Pd(PPh3)4 (16 mg, 0.014 mmol) under nitrogen. The mixture was heated in a microwave oven at 200° C. for 1 h, filtered and purified using preparative HPLC to give N-(4-tert-butyl-2-cyano-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide (476). 1H NMR (400 MHz, DMSO-d6) δ 13.00 (d, J=6.4 Hz, 1H), 12.91 (s, 1H), 10.72 (s, 1H), 8.89 (d, J=6.8 Hz, 1H), 8.34 (d, J=8.2 Hz, 1H), 8.16 (s, 1H), 7.85-7.75 (m, 2H), 7.56-7.54 (m, 1H), 7.44 (s, 1H), 1.35 (s, 9H); HPLC ret. time 3.42 min, 10-100% CH3CN, 5 min gradient; ESI-MS 362.1 m/z (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([NH2:10])[NH:7][C:6]=2[CH:11]=1.N1C=CC=CC=1.[C:18](OC(=O)C)(=[O:20])[CH3:19]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([NH:10][C:18](=[O:20])[CH3:19])[NH:7][C:6]=2[CH:11]=1
Reactant: Nc1nc2ccc(Br)cc2[nH]1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)Nc1nc2ccc(Br)cc2[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 28 %

Procedure:
To a 250 mL round-bottomed flask was added 6-bromo-1H-benzo[d]imidazol-2-amine (2.00 g, 9.43 mmol, Carbocore, The Woodlands, Tex.), DCM (100 mL), pyridine (1.0 mL, 12.3 mmol) and acetic anhydride (0.979 mL, 10.4 mmol). The mixture was stirred at 25° C. for 18 h. The solution was concentrated and then diluted with 10% MeOH (2M in NH3)/CH2Cl2 until homogeneous and then the solution was concentrated onto silica. Purification by silica gel chromatography (0.5 to 5.0% MeOH (2 M in NH3)/CH2Cl2) afforded the title compound as a white solid (0.676 g, 28%). MS (ESI, positive ion) m/z: 254 (M(79Br)+1).
Reaction SMILES: Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:12]=2)=[O:10])[CH2:4]1.C(N(CC)CC)C.[CH3:46][S:47](Cl)(=[O:49])=[O:48]>ClCCl>[CH3:46][S:47]([NH:2][CH:3]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:12]=2)=[O:10])[CH2:4]1)(=[O:49])=[O:48]
Reactant: Cn1nc(-c2cnc3c(n2)c(C(=O)NC2CCC(N)C2)cn3COCC[Si](C)(C)C)c2ccc(Cl)cc21
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cn1nc(-c2cnc3c(n2)c(C(=O)NC2CCC(NS(C)(=O)=O)C2)cn3COCC[Si](C)(C)C)c2ccc(Cl)cc21
Temperature: 0 °C
Reaction time: 8 h
Yield: 78.1 %

Procedure:
In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide hydrochloride (145 mg, 0.23 mmol) was suspended in dichloromethane (2.5 ml). The suspension was cooled to 0° C. and triethylamine (0.10 ml, 0.72 mmol) was added followed by methanesulfonyl chloride (0.02 ml, 0.26 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with dichloromethane (2×). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-5% MeOH) to afford 111 mg (79%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-methanesulfonylamino-cyclopentyl)-amide as a light yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([I:8])[C:3]=1[S:9]([NH2:12])(=[O:11])=[O:10].C(=O)([O-])[O-].[K+].[K+].[CH2:19](I)[CH2:20][CH3:21].O>CN(C)C=O>[I:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([O:1][CH2:19][CH2:20][CH3:21])[C:3]=1[S:9]([NH2:12])(=[O:11])=[O:10]
Reactant: NS(=O)(=O)c1c(O)cccc1I
Reactant: CCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCOc1cccc(I)c1S(N)(=O)=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5.00 g (16.72 mmol) of 2-hydroxy-6-iodobenzenesulfonamide are introduced in 50 ml of dimethylformamide and this initial charge is admixed with 2.54 g (18.39 mmol) of potassium carbonate. This mixture is stirred at room temperature for 1 h. Thereafter 3.13 g (18.39 mmol) of propyl iodide are added dropwise and the reaction mixture is stirred at room temperature for 3 h. It is then poured into water, and the product precipitates out. The solid is washed with water and dried. This gives 4.00 g (70% of theory) of 2-iodo-6-propoxybenzenesulfonamide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:28])([CH3:27])[C:9]([NH:11][NH:12][C:13]([C:15]2[C:16]([CH3:26])=[N:17][C:18]3[C:23]([C:24]=2[CH3:25])=[CH:22][CH:21]=[CH:20][CH:19]=3)=O)=[O:10])=[CH:4][CH:3]=1.COC(CC[N+](S(=O)(=O)N)(CC)CC)=O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:9]2[O:10][C:13]([C:15]3[C:16]([CH3:26])=[N:17][C:18]4[C:23]([C:24]=3[CH3:25])=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:12][N:11]=2)([CH3:27])[CH3:28])=[CH:6][CH:7]=1
Reactant: Cc1nc2ccccc2c(C)c1C(=O)NNC(=O)C(C)(C)c1ccc(Cl)cc1
Agent: CC[N+](CC)(CCC(=O)OC)S(N)(=O)=O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1nc2ccccc2c(C)c1-c1nnc(C(C)(C)c2ccc(Cl)cc2)o1
Temperature: 60 °C
Yield: 36.2 %

Procedure:
To a solution of N′-(2-(4-chlorophenyl)-2-methylpropanoyl)-2,4-dimethylquinoline-3-carbohydrazide (592 mg, 1.5 mmol) in dry tetrahydrofuran (5 ml) was added Burgess's reagent (methoxycarbonyl-sulfamoyltriethylammonium inner salt; 714 mg, 3.0 mmol). The mixture was heated at 60° C. for 1 hour, diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate, and then brine. The organic phase was separated, and the solvent removed under reduced pressure, to provide 2-(2-(4-chlorophenyl)propan-2-yl)-5-(2,4-dimethylquinolin-3-yl)-1,3,4-oxadiazole (205 mg, 36%) as a white powder. 1H NMR (CDCl3, 400 MHz) δ 8.03 (app t, 2H, J=8.2 Hz); 7.78 (app t, 1H, J=7.0 Hz); 7.58 (app t, 1H, J=7.0 Hz); 7.30 (app q, 4H); 2.56 (s, 3H); 2.51 (s, 3H); 1.90 (s, 6H). LCMS (CI) M+H 378.
Reaction SMILES: [CH3:1][C@@:2]1(O)[C@H:9]([CH3:10])[O:8][C@@H:5]([O:6][CH3:7])[CH2:4][C@@H:3]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14].S(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>C1C=CC=CC=1>[CH2:1]=[C:2]1[C@H:9]([CH3:10])[O:8][C@@H:5]([O:6][CH3:7])[CH2:4][C@@H:3]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14]
Reactant: CO[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@](C)(O)[C@H](C)O1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=S(Cl)Cl
Solvent: c1ccccc1
Product: C=C1[C@@H](NC(=O)C(F)(F)F)C[C@H](OC)O[C@H]1C

Procedure:
The starting material for the preparation of the intermediates III-A and III-B is methyl 2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-α-L-lyxo hexopyranoside (VII), a known compound described in British patent application No. 2034707. Treatment of this compound (VII) in anhydrous benzene with thionyl chloride, followed by aqueous sodium bicarbonate gives methyl 2,3,4,6-tetradeoxy-4-C-methylene-3-trifluoroacetamido-α-L-threohexopyranoside (VIII). Catalytic hydrogenation of compound VIII proceeds stereoselectively giving methyl 2,3,4,6-tetradeoxy-4-C-methyl-3-trifluoroacetamido-α-L-arabino-hexopyranoside (XI). Mild acid hydrolysis of compounds VIII and XI gives the corresponding hexopyranoses IX and XII which by treatment with trifluoroacetic anhydride are transformed into the corresponding 1-0-trifluoroacetates X and XIII. Treatment of these intermediates with dry hydrogen chloride in anhydrous diethyl ether leads to the 1-chloroderivatives III-A and III-B, respectively. The foregoing sequence of transformations is shown in the scheme below: ##STR3## For the preparation of the 1-chloroderivative III-C, the key intermediate XVI is obtained by either of two different routes. Oxidation of compound VIII with meta-chloroperbenzoic acid in 1,2-dichloroethane gives compound XVI, which may alternatively be obtained by treatment with diazomethane of methyl 2,3,6-trideoxy-3-trifluoroacetamido-α-L-threo-hexopyranosid-4-ulose (XV), a known compound described in U.S. Pat. No. 4,039,663, as shown below: ##STR4## Azidolysis of methyl 2,3,6-trideoxy-4-C-hydroxymethyl-4,4'-anhydro-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (XVI) gives the azido compound XVII. Catalytic hydrogenation thereof, followed by N-trifluoroacetylation affords compound XVIII, which on mild acid hydrolysis gives XIX. Subsequent 0-trifluoroacetylation thereof, followed by treatment with dry hydrogen chloride in anhydrous diethyl ether gives the 1-chloroderivative III-C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH3:11].FC1C=C([N+]([O-])=O)C=CC=1CBr.FC1C=C([N+]([O-])=O)C=CC=1CP(=O)(OCC)OCC.CC1(C)[O:48][CH:47]([CH2:49][O:50][C:51]2[CH:58]=[CH:57][C:54]([CH:55]=O)=[CH:53][CH:52]=2)[CH2:46][O:45]1>>[OH:48][CH:47]([CH2:46][OH:45])[CH2:49][O:50][C:51]1[CH:58]=[CH:57][C:54]([CH:55]=[CH:11][C:3]2[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=2[F:1])=[CH:53][CH:52]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1F
Reactant: CC1(C)OCC(COc2ccc(C=O)cc2)O1
Agent: CCOP(=O)(Cc1ccc([N+](=O)[O-])cc1F)OCC
Agent: O=[N+]([O-])c1ccc(CBr)c(F)c1
Product: O=[N+]([O-])c1ccc(C=Cc2ccc(OCC(O)CO)cc2)c(F)c1

Procedure:
2-Fluoro-4-nitrotoluene (commercially available) was converted with the use of N-bromosuccimimide into the intermediate 2-fluoro-4-nitrobenzyl bromide, and subsequently into diethyl 2-fluoro-4-nitrobenzylphosphonate, in accordance with the specification of D. H. Wadsworth et al. in the Journal of Organic Chemistry, Vol. 30 (1965) p. 680-685. The title compound was prepared by the same procedure as described in Example 2. Making use of 23.6 g of 4-((2,2-dimethyl-1,3-dioxa-4-cyclopentyl)methyloxy)benzaldehyde and 29.1 g of diethyl 2-fluoro-4-nitrobenzyl phosphonate there were obtained in all 21 g of 4-(2,3-dihydroxypropyloxy)-2'-fluoro-4'nitrostilbene with a melting point of 110° C. and a clearing temperature of 129° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:14](=[O:15])[CH:13]=[CH:12][C:11]([C:16]([O:18][CH3:19])=[O:17])=[CH:10]1>C1COCC1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:14](=[O:15])[CH2:13][CH2:12][C:11]([C:16]([O:18][CH3:19])=[O:17])=[CH:10]1
Reactant: COC(=O)c1ccc(=O)n(-c2c(C)cccc2C)c1
Solvent: C1CCOC1
Product: COC(=O)C1=CN(c2c(C)cccc2C)C(=O)CC1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
In an atmosphere of nitrogen, a 1.0 M diisobutylaluminum hydride THF solution was dropwise added at −78° C. to a THF solution of methyl 1-(2,6-dimethylphenyl)-6-oxo-1,6-dihydropyridine-3-carboxylate. After stirring at −78° C. for 2 hours, the temperature was risen to 0° C., followed by stirring at 0° C. for 1.5 hours. The reaction mixture was warmed up to room temperature, followed by stirring at room temperature for 2 hours. A 1.0 M diisobutylaluminum hydride THF solution was dropwise added to the reaction mixture at 0° C., followed by warming up to room temperature and stirring for 1 hour to obtain methyl 1-(2,6-dimethylphenyl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate. In an atmosphere of nitrogen, lithium aluminum hydride was added to the resulting methyl 1-(2,6-dimethylphenyl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate, while cooling on an ice-methanol bath. Thereafter, by stirring the reaction mixture for 2 hours while heating under reflux, [1-(2,6-dimethylphenyl)piperidin-3-yl]methanol was obtained.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:10]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH2:11][C:12]([NH:14][CH3:15])=O)[CH:8]=2)[CH:3]=[CH:2]1.N1C2C(=CC=CC=2C(C2C=CC=CC=2)CCNC)C=C1>>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:10]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH2:11][CH2:12][NH:14][CH3:15])[CH:8]=2)[CH:3]=[CH:2]1
Reactant: CNC(=O)CC(c1ccc2cc[nH]c2c1)c1c[nH]c2ccccc12
Agent: CNCCC(c1ccccc1)c1cccc2cc[nH]c12
Product: CNCCC(c1ccc2cc[nH]c2c1)c1c[nH]c2ccccc12
Yield: 62 %

Procedure:
The [3-(1H-Indol-6-yl)-3-(1H-indol-3-yl)-propyl]-methyl-amine XXIX (52 mg, 62%) was prepared from 3-(1H-indol-6-yl)-3-(1H-indol-3-yl)-N-methyl-propionamide using the procedure described for [3-(1H-Indol-7-yl)-3-phenyl-propyl]-methyl-amine XX (see Example 4). MS (M+H)=304.
Reaction SMILES: BrC1C(=O)N(CCCCCC)C2C=1C=C1C(=C(Br)C(=[O:20])N1CCCCCC)C=2.C(C(CCCCCCCCCC)C[N:39]1[C:46](C2SC(B3OC(C)(C)C(C)(C)O3)=CC=2)=[C:45]2[C:41](=[C:42](C3SC(B4OC(C)(C)C(C)(C)O4)=CC=3)[N:43](CC(CCCCCCCC)CCCCCCCCCC)[C:44]2=[O:61])[C:40]1=O)CCCCCCC.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1.O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.CO>[O:20]=[C:45]1[C:46]2[C:42]([CH:41]=[CH:40][N:39]=2)=[N:43][C:44]1=[O:61]
Reactant: CCCCCCN1C(=O)C(Br)=c2cc3c(cc21)=C(Br)C(=O)N3CCCCCC
Reactant: CCCCCCCCCCC(CCCCCCCC)CN1C(=O)C2=C(c3ccc(B4OC(C)(C)C(C)(C)O4)s3)N(CC(CCCCCCCC)CCCCCCCCCC)C(=O)C2=C1c1ccc(B2OC(C)(C)C(C)(C)O2)s1
Agent: [Pd]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Agent: F[B-](F)(F)F
Solvent: CO
Solvent: Cc1ccccc1
Solvent: O
Product: O=c1nc2ccnc-2c1=O
Temperature: 25 °C
Yield: 655.1 %

Procedure:
A mixture of 3,7-dibromo-1,5-dihexyl-1H,5H-pyrrolo[2,3-f]indole-2,6-dione (0.075 g, 0.148 mmol), 2,5-dihydro-2,5-bis(2-octyldodecyl)-3,6-bis[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]-pyrrolo[3,4-c]pyrrole-1,4-dione (0.168 g, 0.150 mmol), Pd2(dba)3 (4.0 mg), tri-tert-butylphosphonium tetrafluoroborate (2.0 mg), K3PO4 (0.095 g) and toluene/H2O (8 mL/0.5 mL) was heated at reflux for 48 h. Then after cooling to room temperature, the mixture was dropped into methanol to precipitate. After being filtered and dried, the precipitation was Soxhlet extracted with methanol, acetone, hexane, dichloromethane and chloroform in succession. The chloroform solution was concentrated and reprecipitated in methanol. The solid was filtered and dried to yield polymer (0.130 g, 72.6%) as a black solid.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:13]=[CH:14][C:15]=2[N:16]([CH2:21][CH2:22]O)[S:17]([CH3:20])(=[O:19])=[O:18])[C:9]([O:11][CH3:12])=[O:10])[CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:25][CH2:22][CH2:21][N:16]([C:15]1[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][C:6]=1[O:5][CH2:4][CH:1]1[CH2:3][CH2:2]1)[S:17]([CH3:20])(=[O:19])=[O:18]
Reactant: COC(=O)c1ccc(N(CCO)S(C)(=O)=O)c(OCC2CC2)c1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)c1ccc(N(CCBr)S(C)(=O)=O)c(OCC2CC2)c1
Reaction time: 2 h
Yield: 77 %

Procedure:
To a solution of methyl 3-(cyclopropylmethoxy)-4-(N-(2-hydroxyethyl)-methylsulfonamido)benzoate (0.690 g, 2.009 mmol) in dry DCM (15 ml), CBr4 (0.866 g, 2.61 mmol) was added, followed by triphenylphosphine (0.685 g, 2.61 mmol), and stirring was continued for 2 hours at RT. The solvent was evaporated, and the residue was purified by flash chromatography on silica gel (eluent: EtOAc/petroleum ether 2/8) to give methyl 4-(N-(2-bromoethyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate as a colorless oil (0.630 g, 1.551 mmol, 77% yield, MS/ESI+ 405.8, [MH]+).