Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH2:9])=[CH:4][C:3]=1[N+:16]([O-])=O.C(O)C.[Na+].[SH-]>O>[NH2:16][C:3]1[CH:4]=[C:5]([C:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH2:9])[CH:6]=[CH:7][C:2]=1[NH2:1]
Reactant: C=C(c1ccccc1)c1ccc(N)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [SH-]
Solvent: O
Solvent: CCO
Product: C=C(c1ccccc1)c1ccc(N)c(N)c1
Yield: 83 %

Procedure:
1-(4-Amino-3-nitrophenyl)-1-phenylethylene (7.7 g., 0.032 mole) was dissolved in refluxing ethanol (450 ml.). To this was added, dropwise, a solution of sodium sulfhydrate (38.5 g., 0.45 mole) in water (110 ml.). The resulting solution was refluxed overnight. The solution was diluted with water (1 l.), cooled, and filtered yielding 1-(3,4-diaminophenyl)-1-phenylethylene: 5.6 g., 83% yield, m.p. 109°-110°.
Reaction SMILES: [NH2:1][O:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][O:4]1.C(N(CC)CC)C.[Br:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](Cl)=[O:24]>C(Cl)Cl.CCOC(C)=O>[Br:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([NH:1][O:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][O:4]1)=[O:24]
Reactant: O=C(Cl)CCCCCCBr
Reactant: NOC1CCCCO1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: O=C(CCCCCCBr)NOC1CCCCO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.9 %

Procedure:
to a solution of H2N-OTHP (1.0 g, 8.54 mmol) and triethylamine (2.46 g, 24.39 mmol) in CH2Cl2 (20 mL) was added a solution of 7-bromoheptanoyl chloride (1.84 g, 8.13 mmol) obtained above in CH2Cl2 (10 mL) dropwise cooling in an ice-water bath. The mixture was stirred at room temperature for 1 h. It was diluted with EtOAc and washed with aqueous saturated NaHCO3, water, and brine, before being dried over MgSO4. Filtration and concentration in vacuo and purification by silica gel flash chromatography (n-hexane/EtOAc=3/1) gave 1.3 g (52%) of 7-bromo-N-(tetrahydro-2H-pyran-2-yloxy)-heptanamide as yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:28][C:29]1[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=1[S:37](Cl)(=[O:39])=[O:38]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:11][N:10]=[CH:9][N:8]=1)[S:37]([C:30]1[CH:31]=[C:32]([F:36])[C:33]([F:35])=[CH:34][C:29]=1[F:28])(=[O:39])=[O:38]
Reactant: COc1ccc(CNc2ncns2)c(OC)c1
Reactant: O=S(=O)(Cl)c1cc(F)c(F)cc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc(F)c(F)cc2F)c(OC)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.8 %

Procedure:
To a solution of (N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 14, 13 g, 51.73 mmol) in dry tetrahydrofuran (150 ml) at −70° C. under argon atmosphere was added 1 M lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide in tetrahydrofuran (56.9 ml, 56.9 mmol) dropwise. The reaction mixture was allowed to warm up to room temperature and stirred for 1 h. It was again cooled to −70° C. and a tetrahydrofuran (50 ml) solution of 2,4,5-trifluorobenzenesulfonyl chloride (11.9 g, 51.73 mmol) was added dropwise to it at this temperature. After complete addition, reaction mixture was gradually allowed to warm up to room temperature and stirred for 1 hour. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution. Crude product was purified over 100-200 silica gel using 5-15% v/v ethyl acetate in hexane to give 17 g (75%) of the title compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[C:4]([F:12])[CH:3]=1.S(=O)(=O)(O)O.[CH2:18]=[C:19]([CH3:21])[CH3:20].C(=O)=O>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][C:19]([CH3:21])([CH3:20])[CH3:18])=[O:10])=[C:4]([F:12])[CH:3]=1
Reactant: O=C(O)Cc1ccc(Br)cc1F
Reactant: C=C(C)C
Agent: O=C=O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)Cc1ccc(Br)cc1F
Temperature: 25 °C
Yield: 90 %

Procedure:
Combine 4-bromo-2-fluoro-phenyl acetic acid (15 g, 0.064 mol), dichloromethane (30 mL) and concentrated sulfuric acid (1.1 mL) in a 2 L stainless steel Parr® vessel. Cool the vessel and contents in a dry ice-acetone bath. Freshly distill isobutene (60 mL) with dry ice-acetone condenser and add the isobutene to the cooled Parr® vessel. Seal and pressurize the vessel with nitrogen (20 psig), agitate while allowing the reaction to warm to room temperature and continue agitation at room temperature for 18 hours. Cool the vessel to 10-15° C. with dry ice, vent, and carefully add 150 mL of ice-cold saturated sodium carbonate solution and mix. Decant vessel contents, rinse vessel with dichloromethane (100 mL), agitate mixture and separate the phases. Extract aqueous phase twice with 100 mL portions of dichloromethane, combine organic layers and wash with aqueous saturated sodium chloride, dry over MgSO4 and concentrate to produce 18.61 g (90%) of the title compound as a light orange oil. MS (ES) m/z 288/290, (M+1).
Reaction SMILES: [CH2:1]([N:3]1[C:7]2[C:8]([N+:17]([O-])=O)=[C:9]([Cl:16])[C:10]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:11][C:6]=2[N:5]=[C:4]1[CH3:20])[CH3:2].[H][H]>[Pt]=O.CO>[CH2:1]([N:3]1[C:7]2[C:8]([NH2:17])=[C:9]([Cl:16])[C:10]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:11][C:6]=2[N:5]=[C:4]1[CH3:20])[CH3:2]
Reactant: [H][H]
Reactant: CCn1c(C)nc2cc(S(C)(=O)=O)c(Cl)c([N+](=O)[O-])c21
Agent: O=[Pt]
Solvent: CO
Product: CCn1c(C)nc2cc(S(C)(=O)=O)c(Cl)c(N)c21
Temperature: 25 °C
Reaction time: 22.5 h

Procedure:
1-Ethyl-2-methyl-5-methylsulfonyl-6-chloro-7-nitrobenzimidazole (2.50 g.) was combined with 75 ml. of methanol and 0.2 g. of 87% platinum oxide catalyst in a hydrogenation bottle. The bottle was charged with 37 psi of hydrogen and shaken at room temperature for 22.5 hours. The resultant reaction mixture was filtered to remove the catalyst and the filtrate evaporated to dryness under reduced pressure to give 2.27 g. (100%) of the desired 7-amino derivative, melting at 179°-186° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.Cl[C:13]1[CH:18]=[N:17][CH:16]=[CH:15][N:14]=1>C1(C)C=CC=CC=1>[N:14]1[CH:15]=[CH:16][N:17]=[CH:18][C:13]=1[NH:1][C:2]1[CH:7]=[N:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][CH:3]=1
Reactant: Nc1ccc(C(F)(F)F)nc1
Reactant: Clc1cnccn1
Solvent: Cc1ccccc1
Product: FC(F)(F)c1ccc(Nc2cnccn2)cn1
Temperature: 95 °C

Procedure:
To a solution of 5-amino-2-trifluoromethylpyridine (0.81 g) in 3 Ml toluene was added chloropyrazine (0.45 Ml, 1.0 equiv) via syringe. The homogeneous solution was heated to 95° C., then cooled to room temperature and concentrated in vacuo. Purification by silica gel chromatography (40% EtOAc in hexanes) afforded the title compound: 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 7.5 (s, 1 H) 7.6 (s, 1 H) 8.0 (s, 1 H) 8.2 (s, 1 H) 8.4 (s, 2 H) 8.8 (s, 1 H); (M+H)+ 241.1.
Reaction SMILES: C([O:9]/[C:10](/[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:11]\[C:12]1[N:16](C(=O)C2C=CC=CC=2)[C:15]2[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=2[N:13]=1)(=O)C1C=CC=CC=1>Cl>[NH:13]1[C:14]2[CH:28]=[CH:27][CH:26]=[CH:25][C:15]=2[N:16]=[C:12]1[CH2:11][C:10]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:9]
Reactant: O=C(O/C(=C\c1nc2ccccc2n1C(=O)c1ccccc1)c1ccccc1)c1ccccc1
Agent: Cl
Product: O=C(Cc1nc2ccccc2[nH]1)c1ccccc1
Yield: 152.4 %

Procedure:
5.73 g (0.01 mol) of the compound of Example I are refluxed 2 h in 115 ml concentrated hydrochloric acid. The mixture is cooled to rT and concentrated under vacuum. The residue is washed with petrol ether and the product is filtered, stirred with toluene and filtered again, washed with petrol ether, filtered and dried to yield 3.6 g (96% o.th.) 2-(1H-Benzimidazol-2-yl)-1-phenylethanone.
Reaction SMILES: [C:1](OC)([O:5][CH3:6])([O:3]C)[CH3:2].[CH3:9][C:10]([CH3:14])=[CH:11][CH2:12]O.P(=O)(O)(O)O>CO>[CH3:9][C:10]([CH3:14])([CH:11]=[CH2:12])[CH2:2][C:1]([O:5][CH3:6])=[O:3]
Reactant: CC(C)=CCO
Reactant: COC(C)(OC)OC
Agent: O=P(O)(O)O
Solvent: CO
Product: C=CC(C)(C)CC(=O)OC
Yield: 40.5 %

Procedure:
A mixture of trimethyl orthoacetate (120 g; 1 mole), 3-methylbut-2-enol (21.5 g; 0.25 mole) and orthophosphoric acid (1.5 g; 0.015 mole) was placed in a flask equipped with a stirrer and a 10 cm fractionating column packed with Fenske rings. The mixture was heated, with stirring, to a temperature of 95° to 110° C. and maintained at this temperature for a period of 2 hours while the methanol formed was collected by distillation. The excess trimethyl orthoacetate was distilled from the reaction mixture over a period of 1 hour during which time the temperature of the reaction mixture was raised to 140°-145° C. The reaction mixture was heated with stirring, at a temperature of 140°-145° C. for a period of 1 hour and then product was distilled to give methyl 3,3-dimethylpent-4-enoate (14.4 g; 40.6%); bp 95°-99° C. at 140 mm Hg.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][CH2:10][C:11]([NH:13][C@H:14]([C:24]([NH:26][C@H:27]([C:35]([NH:37][C@H:38]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C@@H:39]([CH3:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:36])[C@@H:28]([CH3:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:25])[CH2:15][CH2:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:12])=[O:8])=[O:4]>CO.[H][H].[C].[Pd]>[NH2:1][CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][CH2:10][C:11]([NH:13][C@H:14]([C:24]([NH:26][C@H:27]([C:35]([NH:37][C@H:38]([C:46]([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:47])[C@@H:39]([CH3:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:36])[C@@H:28]([CH3:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:25])[CH2:15][CH2:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:12])=[O:8])=[O:4]
Reactant: [H][H]
Reactant: C[C@@H](OC(C)(C)C)[C@H](NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)CNC(=O)CNC(=O)CNC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)OC(C)(C)C)[C@@H](C)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: C[C@@H](OC(C)(C)C)[C@H](NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)CNC(=O)CNC(=O)CN)C(=O)N[C@H](C(=O)OC(C)(C)C)[C@@H](C)OC(C)(C)C

Procedure:
Z-Gly-Gly-Gly-Glu(OtBu)-Thr(tBu)-Thr(tBu)-OtBu (SEQ ID No. 12) (1.97 g, 2.24 mmol) obtained in Example 4-IV) was dissolved in methanol (60 ml). To the solution was added 10% palladium-carbon (120 mg), and the mixture was stirred for 2 hours in hydrogen streams at 20° C. under 1 atom. The catalyst was removed, then the solvent was distilled off to leave H-Gly-Gly-Gly-Glu(OtBu)-Thr(tBu)-Thr(tBu)-OtBu (SEQ ID No. 81) as a solid product.
Reaction SMILES: [Cl-].C(CC(CC)(NC(C)C)C)C.[Si:13]([O:20][CH2:21][C:22]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])=[C:24](Cl)[CH:23]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>>[Si:13]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])=[CH:26][C:27]=1[O:28][CH3:29])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15]
Reactant: C=CC(=O)Nc1cc(OC)c(CO[Si](C)(C)C(C)(C)C)cc1Cl
Agent: CCCC(C)(CC)NC(C)C
Agent: [Cl-]
Product: C=CC(=O)Nc1ccc(CO[Si](C)(C)C(C)(C)C)c(OC)c1

Procedure:
Obtained as a solid (63%) from [4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-methoxyphenyl]amine (intermediate 99; 5 g, 18.7 mmol), acryloil chloride (1.98 mL, 24.28 mmol) and diethyldiisopropylamine (4.9 mL, 28.06 mmol) following the experimental procedure as described in intermediate 40. The crude obtained was purified by column chromatography with silica gel, eluting with methylene chloride.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[S:17][C:16]([N:18]3[CH2:25][C:24]4[CH2:23][NH:22][CH2:21][C:20]=4[CH2:19]3)=[N:15][CH:14]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C([O-])=O.[Br:33][C:34]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][C:35]=1[C:36](O)=[O:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[S:17][C:16]([N:18]3[CH2:25][C:24]4[CH2:23][N:22]([C:36](=[O:37])[C:35]5[CH:39]=[C:40]([O:43][CH3:44])[CH:41]=[CH:42][C:34]=5[Br:33])[CH2:21][C:20]=4[CH2:19]3)=[N:15][CH:14]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(NCCCc1ccccc1)c1cnc(N2CC3=C(CNC3)C2)s1
Reactant: COc1ccc(Br)c(C(=O)O)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])C(F)(F)F
Product: COc1ccc(Br)c(C(=O)N2CC3=C(C2)CN(c2ncc(C(=O)NCCCc4ccccc4)s2)C3)c1

Procedure:
N-(3-Phenylpropyl)-2-(3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl)thiazole-5-carboxamide, trifluoroacetate (44.6 mg, 0.095 mmol) was reacted with 2-bromo-5-methoxybenzoic acid after activation with HATU analogously to example 3f. M+H+: 567.17.
Reaction SMILES: [OH:1][C@@H:2]([C@@H:9]([NH:14][C:15]([C@H:17]1[O:19][C@@H:18]1[C:20]([O:22]CC)=[O:21])=[O:16])[CH2:10][CH:11]([CH3:13])[CH3:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[K+].C(O)C.O.Cl>C(O)C>[OH:1][C@@H:2]([C@@H:9]([NH:14][C:15]([C@H:17]1[O:19][C@@H:18]1[C:20]([OH:22])=[O:21])=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)[C@H](O)c1ccccc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)C[C@H](NC(=O)[C@H]1O[C@@H]1C(=O)O)[C@H](O)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of ethyl (2S,3S)-3-[[1-(S)-[α-(R)-hydroxybenzyl]-3-methylbutyl]carbamoyl]oxirane-2-carboxylate (558 mg, 1.66 mmol.) in ethanol (4 mL) was dropwise added 0.5N potassium hydroxide/ethanol solution (4.0 mL, 2.0 mmol.) under chilling with ice. The mixture was stirred for 4 hours at room temperature, and made acidic to reach pH 1-2 by addition of water (40 mL) and 2N hydrochloric acid (approx. 2 mL). The acidic mixture was extracted with three portions of ethyl acetate. The three extracts were combined and washed successively with water and an aqueous saturated sodium chloride solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give the titled compound as a white amorphous product (490 mg, yield 96%).
Reaction SMILES: [NH2:1][C:2]1[N:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].Br[C:23]1[C:24]([Cl:49])=[C:25]2[C:31]([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=3[O:39][CH3:40])=[CH:30][N:29]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:26]2=[N:27][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[NH2:1][C:2]1[N:12]=[CH:11][C:10]([C:23]2[C:24]([Cl:49])=[C:25]3[C:31]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=4[O:39][CH3:40])=[CH:30][N:29]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:26]3=[N:27][CH:28]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:7])[CH3:8])=[O:5]
Reactant: COc1cc(Cl)ccc1-c1cn(COCC[Si](C)(C)C)c2ncc(Br)c(Cl)c12
Reactant: CN(C)C(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cnc1N
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(Cl)ccc1-c1cn(COCC[Si](C)(C)C)c2ncc(-c3cnc(N)c(C(=O)N(C)C)c3)c(Cl)c12
Yield: 55 %

Procedure:
Into a 20 mL Personal Chemistry microwave reaction vial were added 2-Amino-N,N-dimethyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinamide (1.55 g, 5.35 mmol), 5-Bromo-4-chloro-3-(4-chloro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (1.58 g, (3.15 mmol), bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (129 mg, 0.158 mmol), sodium carbonate solution (3.15 mL, 6.30 mmol, 2.0 M solution in water) and N,N-dimethylformamide (15 mL). The vial was purged with nitrogen, sealed, and irradiated in a Personal Chemistry Optimizer at 120° C. for 30 minutes. The mixture was concentrated in vacuo. The crude was taken up in dichloromethane (150 mL) and washed with aqueous saturated sodium carbonate solution (1×150 mL) and brine (1×150 mL). The organ phase was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 2-Amino-5-[4-chloro-3-(4-chloro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-nicotinamide (1.02 g, 1.74 mmol, 55% yield). 1H-NMR [500 MHz, d6-DMSO] δ: 8.26 (s, 1H), 8.06 (d, 1H), 7.72 (s, 1H), 7.48 (d, 1H), 7.26 (d, 1H), 7.11 (d, 1H), 7.03 (dd, 1H), 6.18 (s, 2H), 5.66 (s, 2H), 3.71 (s, 3H), 3.59 (t, 2H), 2.94 (s, 6H), 0.85 (s, 2H), −0.08 (s, 8H); MS [MH+] m/z: 486
Reaction SMILES: [C:1]1([N:7]2[C:23](=[O:24])[C:22]3[C:21]4[C:20]5[C:15](=[CH:16][CH:17]=[C:18]([O:25][CH3:26])[CH:19]=5)[N:14]([CH2:27][O:28][CH3:29])[C:13]=4[C:12]([CH:30]=O)=[CH:11][C:10]=3[C:8]2=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[CH3:33][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].C(OCC)(=O)C>CN(C)C=O.O>[C:1]1([N:7]2[C:23](=[O:24])[C:22]3[C:21]4[C:20]5[C:15](=[CH:16][CH:17]=[C:18]([O:25][CH3:26])[CH:19]=5)[N:14]([CH2:27][O:28][CH3:29])[C:13]=4[C:12]([CH:30]=[CH2:33])=[CH:11][C:10]=3[C:8]2=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COCn1c2ccc(OC)cc2c2c3c(cc(C=O)c21)C(=O)N(c1ccccc1)C3=O
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: C=Cc1cc2c(c3c4cc(OC)ccc4n(COC)c13)C(=O)N(c1ccccc1)C2=O
Yield: 87.1 %

Procedure:
150 mg of N-phenyl-1-formyl-6-methoxy-9-methoxymethylcarbazole-3,4-dicarboximide and 220 mg of methyltriphenylphosphonium iodide were dissolved in N,N-dimethylformamide. Thereto was added 20 mg of 60% sodium hydride with stirring under ice cooling. The resulting mixture was stirred at the same temperature for 30 minutes. To the reaction mixture were added 100 ml of ethyl acetate and 50 ml of water. The organic layer was separated, washed with 50 ml of water and an aqueous saturated sodium chloride solution in this order and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: benzene/ethyl acetate=50/1 to 20/1) to obtain 130 mg (yield: 87%) of N-phenyl-6-methoxy-9-methoxymethyl-1-vinylcarbazole-3,4-dicarboximide.
Reaction SMILES: [Cl:1][C:2]1[NH:6][C:5](C(O)=O)=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]>C(O)CO.O.C(OCC)(=O)C>[Cl:1][C:2]1[NH:6][CH:5]=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Cl)[nH]1
Solvent: CCOC(C)=O
Solvent: O
Solvent: OCCO
Product: O=[N+]([O-])c1cc[nH]c1Cl
Yield: 79.6 %

Procedure:
A stirred solution of 0.34 gram (0.0018 mole) of 5-chloro-4-nitropyrrole-2-carboxylic acid in about 5 mL of ethylene glycol was heated to 190° C. where it was maintained during a one-hour period. After this time the reaction mixture was cooled and diluted with 20 mL of water and 25 mL of ethyl acetate. The organic layer was separated and washed with 25 mL of a solution of 12.5 mL of water and 12.5 mL of an aqueous solution saturated with sodium bicarbonate. The organic layer was then dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using diethyl ether as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.21 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[C:8]([CH2:10][CH3:11])[C:7]([CH:12]([C:14]2[N:15]=[CH:16][N:17](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:18]=2)O)=[C:6]([CH2:38][CH3:39])[CH:5]=1)[CH3:2].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([CH2:10][CH3:11])[C:7]([CH2:12][C:14]2[N:15]=[CH:16][NH:17][CH:18]=2)=[C:6]([CH2:38][CH3:39])[CH:5]=1)[CH3:2]
Reactant: CCOc1cc(CC)c(C(O)c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)c(CC)c1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOc1cc(CC)c(Cc2c[nH]cn2)c(CC)c1

Procedure:
Prepared in analogy to Example 57(e) from rac-(4-ethoxy-2,6-diethyl-phenyl)-(1-trityl-1H-imidazol-4-yl)-methanol, triethylsilane and trifluoroacetic acid in dichloromethane in a pressure tube at 70° C. for 16 h. White crystalline solid. MS (ISP): 259.4 ([M+H]+).
Reaction SMILES: Cl.[NH:2]1[C:7]2[N:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5]2([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[O:4][C:3]1=[O:17].Cl[C:19]1[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([C:26]([C:28]2[CH:38]=[C:37]([CH3:39])[C:31]3[N:32]([CH3:36])[C:33](=[O:35])[O:34][C:30]=3[CH:29]=2)=[O:27])[CH:20]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:36][N:32]1[C:31]2[C:37]([CH3:39])=[CH:38][C:28]([C:26]([C:21]3[N:22]=[C:23]([CH3:25])[N:24]=[C:19]([N:14]4[CH2:13][CH2:12][C:5]5([O:4][C:3](=[O:17])[NH:2][C:7]6[N:8]=[CH:9][CH:10]=[CH:11][C:6]5=6)[CH2:16][CH2:15]4)[CH:20]=3)=[O:27])=[CH:29][C:30]=2[O:34][C:33]1=[O:35]
Reactant: O=C1Nc2ncccc2C2(CCNCC2)O1
Reactant: Cc1nc(Cl)cc(C(=O)c2cc(C)c3c(c2)oc(=O)n3C)n1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(C(=O)c2cc(C)c3c(c2)oc(=O)n3C)cc(N2CCC3(CC2)OC(=O)Nc2ncccc23)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
77 mg (0.30 mmol) spiro[piperidin-4,4′-pyrido[2,3-d][1,3]oxazin]-2′(1′H)-one hydrochloride, 88 mg (0.28 mmol) 6-(6-chloro-2-methyl-pyrimidin-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one and 0.17 mL (1.0 mmol) DIPEA were combined in 2 mL DMF and stirred overnight at RT. Then the reaction mixture was purified by preparative HPLC-MS. The fractions containing the product were combined and the organic solvent was evaporated down. The residue was neutralised with 4N aqueous sodium hydroxide solution. The precipitate formed was suction filtered, washed with water and dried i. vac.
Reaction SMILES: [CH2:1]([N:3]1[CH2:6][CH:5]([O:7][C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=2)[CH2:4]1)[CH3:2]>C(O)C.[Pd]>[NH2:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][CH:5]2[CH2:4][N:3]([CH2:1][CH3:2])[CH2:6]2)=[CH:9][CH:10]=1
Reactant: CCN1CC(Oc2ccc([N+](=O)[O-])cc2)C1
Agent: [Pd]
Solvent: CCO
Product: CCN1CC(Oc2ccc(N)cc2)C1

Procedure:
A solution of 1-ethyl-3-(4-nitrophenoxy)azetidine in ethanol is subjected to catalytic reduction using palladium on carbon catalyst using standard procedures to obtain the title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[O:20][C:18](=[O:19])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C([N-]C(C)C)(C)C.[Li+].[CH2:29](Br)[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C1(C)C=CC=CC=1.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[CH2:29]([C@H:17]1[CH2:16][C@@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])=[CH:14][CH:13]=2)[O:20][C:18]1=[O:19])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCBr
Reactant: CCCCCCCOc1ccc([C@@H]2CCC(=O)O2)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCCCCCCOc1ccc([C@@H]2C[C@H](CCCCCC)C(=O)O2)cc1
Temperature: -65 °C
Yield: 1.3 %

Procedure:
Rel-(S)-γ-(4-heptyloxyphenyl)-γ-butyrolactone (3.0 g) and anhydrous tetrahydrofuran (50 ml) were placed in a 200 ml three-necked flask, followed by cooling the mixture down to -65° C. with stirring, dropwise adding a tetrahydrofuran solution of lithium diisopropylamide (21.8 mmol) (hereinafter abbreviated to LDA) over 30 minutes, cooling down to -65° C. with stirring for one hour, dropwise adding a mixed solution of hexylbromide (2.71 g), hexamethylphosphoric triamide (hereinafter abbreviated to HMPA) (2.93 g) and anhydrous tetrahydrofuran (5 ml) over 20 minutes, gradually raising the temperature, agitating the mixture at room temperature overnight, adding ice water (50 ml) and toluene (200 ml), washing the resulting organic layer with 2N-hydrochloric acid, saturated NaHCOs aqueous solution and saturated NaCl aqueous solution in this order, drying the organic layer over anhydrous magnesium sulfate, removing magnesium sulfate, concentrating the organic layer under reduced pressure, separation-purifying according to chromatography and recrystallizing from ethanol, to obtain rel-(αS,γS)-α-hexyl-γ-(4-heptyloxyphenyl)-γ-butyrolactone (cis-form) (0.05 g). m.p.: 74.8°-75.8° C.