Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([CH2:4][C:5]([OH:7])=[O:6])=O.[OH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)([CH3:17])[CH3:16])=[CH:11][CH:10]=1.C([O-])(=[O:27])C>C1(OC2C=CC=CC=2)C=CC=CC=1>[C:5]([O-:7])(=[O:6])[C:4]1[CH:18]=[CH:23][C:22]([C:21]([O-:24])=[O:27])=[CH:1][CH:2]=1.[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([C:18]2[CH:19]=[CH:20][C:21]([OH:24])=[CH:22][CH:23]=2)([CH3:17])[CH3:16])=[CH:13][CH:14]=1
Reactant: CC(=O)[O-]
Reactant: CC(=O)CC(=O)O
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: O=C([O-])c1ccc(C(=O)[O-])cc1
Temperature: 290 °C

Procedure:
In a 0.5 liter flask equipped wiht a stirrer, thermometer, a distillation set-up and an argon inlet tube are placed 15.617 gms (0.05 mole) of the diacetate of bisphenol-A, 0.05 moles of the acetate of the monofunctional polyphenylene oxide prepared in Example 1, possessing a molecular weight of about 5,500 and having the structure: ##STR11## and 6.04 (0.037 moles) of each terephthalic and isophthalic acids. To this mixture are added about 100 ml of diphenyl ether. Heating, stirring and argon circulation are started. When the temperature reaches about 250° C. strong distillation of acetic acid is observed. The reaction mixture is gradually heated to 290° C. with continuous distillation of acetic acid and diphenyl ether. After 5 hrs a very viscous melt is obtained (290° C.). The melt is cooled and finely ground. A quantitative yield of a slightly yellow copolymer of polyphenylene oxide and the poly(iso/terephthalate) (1:1) of bisphenol-A results.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[NH:10][CH3:11])([O-])=O>C(O)C.[Pt]=O>[NH2:1][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[NH:10][CH3:11]
Reactant: CNc1ccncc1[N+](=O)[O-]
Agent: O=[Pt]
Solvent: CCO
Product: CNc1ccncc1N
Temperature: 25 °C
Reaction time: 7.5 h
Yield: 79.7 %

Procedure:
150 mg of platinum oxide was added to 10 ml of a solution of 3-nitro-4-methylaminopyridine (1.5 g) in ethanol. The mixture was stirred under a hydrogen atmosphere at room temperature for 7.5 hours. Platinum oxide was removed by filtration, and the filtrate was concentrated. Thus, 962 mg (yield: 80%) of the intended product was obtained as brown crude crystals.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]([CH2:12][CH3:13])([CH2:7][NH:8][CH:9]([CH3:11])[CH3:10])[CH2:5][CH3:6].[C:15]1(=O)CCC[CH2:16]1>>[CH3:1][O:2][C:3](=[O:14])[C:4]([CH2:7][NH:8][CH:9]1[CH2:10][CH2:16][CH2:15][CH2:11]1)([CH2:12][CH3:13])[CH2:5][CH3:6]
Reactant: CCC(CC)(CNC(C)C)C(=O)OC
Reactant: O=C1CCCC1
Product: CCC(CC)(CNC1CCCC1)C(=O)OC

Procedure:
The title compound was prepared by an analogous method to the preparation of Intermediate 200, on a 50 mmol scale utilising Cyclopentanone (Aldrich; 6.33 g, 75 mmol), and distillation at 50° C. and 0.53 mbar pressure, as a clear oil (7.5 g, 65%)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9](O)[CH2:10][O:11][CH3:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:14]1(=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16](=[O:23])[NH:15]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([N:15]2[C:16](=[O:23])[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:14]2=[O:24])[CH2:10][O:11][CH3:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COC[C@H](O)c1ccc(Cl)c(Cl)c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC[C@H](c1ccc(Cl)c(Cl)c1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 20 h
Yield: 96 %

Procedure:
To a solution of 194 (1.25 g, 5.65 mmol) and THF (10 mL) at RT was added sequentially isoindoline-1,3-dione (0.915 g, 6.22 mmol) and PPh3 (2.22 g, 8.48 mmol) followed by the dropwise addition of DEAD (3.34 mL, 8.48 mmol). The reaction was warmed to RT, stirred for 20 h and then concentrated to dryness. Ether (300 mL) was added, and the resulting solid was filtered and discarded. The filtrate was then poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with DCM to afford 1.9 g (96.0%) of (S)-2-(1-(3,4-dichlorophenyl)-2-methoxyethyl)isoindoline-1,3-dione (196).
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[F:5][C:6]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:7]=1[O:8][C:9]1[C:10]2[N:11]([CH:15]=[CH:16][CH:17]=2)[N:12]=[CH:13][CH:14]=1.[C:25](Cl)(=[O:27])[CH3:26].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[F:5][C:6]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:7]=1[O:8][C:9]1[C:10]2[N:11]([CH:15]=[CH:16][C:17]=2[C:25](=[O:27])[CH3:26])[N:12]=[CH:13][CH:14]=1
Reactant: CC(=O)Cl
Reactant: O=[N+]([O-])c1ccc(Oc2ccnn3cccc23)c(F)c1
Agent: O=C([O-])O
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: CC(=O)c1ccn2nccc(Oc3ccc([N+](=O)[O-])cc3F)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.7 %

Procedure:
AlCl3 (1.46 g, 10.98 mmol) was added to a solution of 4-(2-fluoro-4-nitrophenoxy)pyrrolo[1,2-b]pyridazine (600 mg, 2.19 mmol) in dichloroethane (60 mL). After stirring at room temperature for 1 hour and adding acetyl chloride (0.17 mL, 2.42 mmol), the mixture was further stirred for 3 hours. The resulting reaction mixture was neutralized with saturated sodium bicarbonate aqueous solution. The resulting mixture was filtered through celite. After phase separation of the filtrate, the organic layer was dried with magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel chromatography (1-6% ethyl acetate in dichloromethane) to give the target compound as a white solid (640 mg, 2.03 mmol, 93% yield).
Reaction SMILES: [OH:1][CH:2]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:3]1[CH:4]=[C:5]([C:16](O)=[O:17])[CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH:8]=1.Cl.Cl.[CH3:27][C:28]1[N:33]=[CH:32][C:31]([C@H:34]([NH2:36])[CH3:35])=[CH:30][CH:29]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:1][CH:2]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:3]1[CH:4]=[C:5]([C:16]([NH:36][C@@H:34]([C:31]2[CH:32]=[N:33][C:28]([CH3:27])=[CH:29][CH:30]=2)[CH3:35])=[O:17])[CH:6]=[C:7]([C:9]2[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=2)[CH:8]=1
Reactant: Cc1ccc([C@@H](C)N)cn1
Reactant: Cc1ccc(-c2cc(C(=O)O)cc(C(O)c3ccccc3)c2)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-c2cc(C(=O)N[C@H](C)c3ccc(C)nc3)cc(C(O)c3ccccc3)c2)cc1
Temperature: 30 °C
Reaction time: 16 h

Procedure:
To a solution of 5-(hydroxy(phenyl)methyl)-4′-methylbiphenyl-3-carboxylic acid (50 mg, 0.16 mmol) in N,N-dimethylformamide (1 mL) were added (R)-1-(6-methylpyridin-3-yl)ethanamine dihydrochloride (70 mg, 0.34 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (120 mg, 0.32 mmol) and N,N-diisopropylethylamine (500 μL, 2.87 mmol). The reaction mixture was stirred for 16 hours at 30° C. The reaction mixture was purified by preparative HPLC (100×21.2 mm C18 column, CH3CN/water[1 mM Et2NH]) to afford a light color solid.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C[Si](C)(C)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.[Ag-]=O.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>[N:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)c1ccccn1
Reactant: COC(=O)C1CCN(S(=O)(=O)c2ccc(I)cc2)CC1
Agent: O=[Ag-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: COC(=O)C1CCN(S(=O)(=O)c2ccc(-c3ccccn3)cc2)CC1
Temperature: 90 °C
Yield: 50 %

Procedure:
To a stirred suspension of methyl 1-[(4-iodophenyl)sulfonyl]piperidine-4-carboxylate (1.97 g, 4.81 mmol) and 2-(trimethylsilyl)pyridine (2.0 mL), 14.5 mmol) in anhydrous N,N-dimethyl formamide (50 mL) is added silver (I) oxide (1.12 g, 4.82 mmol), tetrakis(triphenylphosphine)palladium (0.28 g, 5 mol %) and tetrabutyl ammonium fluoride (1M in THF, 0.48 mL). The reaction is heated at 90° C. for 18 h. The reaction mixture is filtered and washed with EtOAc. The filtrate is concentrated under reduced pressure. Purification by column chromatography (silica, eluent: heptane, 5-75% EtOAc) gives 0.87 g (50%) of methyl 1-{[4-(pyridin-2-yl)phenyl]sulfonyl}piperidine-4-carboxylate. m/z=361 [M++H].
Reaction SMILES: ClC1C=CC(C2NC(C3C=CC([O:19]C)=CC=3OCC)=NC2CC)=CC=1.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]2[N:37]([C:38]([N:40]3[CH2:45][CH2:44][N:43](C)[CH2:42][CH2:41]3)=[O:39])[C:36]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=3[O:55][CH2:56][CH3:57])=[N:35][CH:34]2[CH2:58][CH:59]2CCCC2)=[CH:29][CH:28]=1>>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH:33]2[N:37]([C:38]([N:40]3[CH2:41][CH2:42][NH:43][C:44](=[O:19])[CH2:45]3)=[O:39])[C:36]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=3[O:55][CH2:56][CH3:57])=[N:35][CH:34]2[CH2:58][CH3:59])=[CH:31][CH:32]=1
Reactant: CCOc1cc(OC)ccc1C1=NC(CC)C(c2ccc(Cl)cc2)N1
Reactant: CCOc1cc(OC)ccc1C1=NC(CC2CCCC2)C(c2ccc(Cl)cc2)N1C(=O)N1CCN(C)CC1
Product: CCOc1cc(OC)ccc1C1=NC(CC)C(c2ccc(Cl)cc2)N1C(=O)N1CCNC(=O)C1

Procedure:
4-[5-(4-Chloro-phenyl)-2-(2-ethoxy-4-methoxy-phenyl)-4-ethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one was prepared from 5-(4-chloro-phenyl)-2-(2-ethoxy-4-methoxy-phenyl)-4-ethyl-4,5-dihydro-1H-imidazole (Example 20) in an analogous manner as described for the preparation of [5-(4-chloro-phenyl)-4-cyclopentylmethyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-(4-methyl-piperazin-1-yl)-methanone (Example 24). HR-MS (ES, m/z) observed 485.1959, calculated for C25H30N4O3Cl [(M+H)+]485.1950.
Reaction SMILES: F[C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.Cl.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([CH:24]3[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]3)[O:21][N:20]=2)=[CH:15][CH:14]=1>C(Cl)Cl.CO>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([CH:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:6]([C:5]4[CH:9]=[CH:10][CH:2]=[CH:3][CH:4]=4)=[O:7])[CH2:25]3)[O:21][N:20]=2)=[CH:15][CH:14]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: Fc1ccc(-c2noc(C3CCCNC3)n2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: O=C(c1ccccc1)N1CCCC(c2nc(-c3ccc(F)cc3)no2)C1
Yield: 30 %

Procedure:
The compound was prepared following the procedure described in the Example 3 (D), using 4-Fluoro-benzoyl chloride as the acyl chloride of choice and the 3-[3-(4-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidine hydrochloride (already prepared before in the Example 4 (B)). Yield: 30% (white powder); mp=82-83° C.; Rf=0.25 DCM/MeOH:98/2);
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([CH2:10][OH:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(N(CC)CC)C>C(Cl)Cl.CS(C)=O>[F:1][C:2]1[CH:9]=[C:8]([CH:10]=[O:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: N#Cc1ccc(CO)cc1F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: N#Cc1ccc(C=O)cc1F
Reaction time: 1 h

Procedure:
2-Fluoro-4-hydroxymethylbenzonitrile (as described in Example 9, Step C) (10 g, 0,066 mol) and triethylamine (32.3 mL, 0.231 mol) were dissolved in CH2Cl2 (100 mL)-DMSO (20 mL) at <5° C. with stirring and treated dropwise with a solution of pyridine•SO3 complex (31.5 g, 0.198 mol) in DMSO (70 mL). The reaction mixture was maintained at a temperature <10° C. The reaction mixture was stirred at 5° C. for 1 hr after the addition, then at 20° C. for 1 hr, then partitioned between CH2Cl2 and H2O. The organic layer was separated, washed well with H2O, brine, and dried (Na2SO4). Filtration and concentration gave the title compound after purification by chromatography (silica gel, hexane:EtOAc, 3:1).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[N:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=4[C:10]=3[NH:9][C:8]2=[O:20])[CH2:3][CH2:2]1.Cl[C:22]1[N:27]=[CH:26][N:25]=[C:24]([C:28]([C:30]2[CH:40]=[C:39]([CH3:41])[C:33]3[N:34]([CH3:38])[C:35](=[O:37])[O:36][C:32]=3[CH:31]=2)=[O:29])[CH:23]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:38][N:34]1[C:33]2[C:39]([CH3:41])=[CH:40][C:30]([C:28]([C:24]3[N:25]=[CH:26][N:27]=[C:22]([N:1]4[CH2:2][CH2:3][CH:4]([N:7]5[C:11]6[CH:12]=[N:13][C:14]7[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=7[C:10]=6[NH:9][C:8]5=[O:20])[CH2:5][CH2:6]4)[CH:23]=3)=[O:29])=[CH:31][C:32]=2[O:36][C:35]1=[O:37]
Reactant: O=c1[nH]c2c3ccccc3ncc2n1C1CCNCC1
Reactant: Cc1cc(C(=O)c2cc(Cl)ncn2)cc2oc(=O)n(C)c12
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)c2cc(N3CCC(n4c(=O)[nH]c5c6ccccc6ncc54)CC3)ncn2)cc2oc(=O)n(C)c12

Procedure:
0.11 g (0.40 mmol) 3-piperidin-4-yl-1,3-dihydroimidazo[4,5-c]quinolin-2-one, 0.12 g (0.40 mmol) 6-(6-chloropyrimidine-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one and 0.14 mL (0.80 mmol) DIPEA were stirred overnight in 3 mL DMF at RT. The mixture was purified by preparative HPLC-MS. The fractions containing the product were combined, the organic solvent was eliminated i. vac. and the aqueous phase remaining was neutralised with 4M aqueous NaOH solution. The precipitate was suction filtered, washed with water and dried i. vac.
Reaction SMILES: O[C:2]1[C:3]2[N:11]=[CH:10][CH:9]=[C:8]([C:12]([NH2:14])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1.Cl.[N:16]1([CH2:20][C@@H:21]([NH2:32])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([CH:29]([F:31])[F:30])[CH:23]=2)[CH2:19][CH2:18][CH2:17]1>>[N:16]1([CH2:20][C@@H:21]([NH:32][C:2]2[C:3]3[N:11]=[CH:10][CH:9]=[C:8]([C:12]([NH2:14])=[O:13])[C:4]=3[N:5]=[CH:6][N:7]=2)[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([CH:29]([F:30])[F:31])[CH:23]=2)[CH2:19][CH2:18][CH2:17]1
Reactant: N[C@H](CN1CCC1)c1ccc(F)c(C(F)F)c1
Reactant: NC(=O)c1ccnc2c(O)ncnc12
Agent: Cl
Product: NC(=O)c1ccnc2c(N[C@H](CN3CCC3)c3ccc(F)c(C(F)F)c3)ncnc12

Procedure:
Compound 48 was prepared following general synthesis scheme 7 wherein 4-hydroxypyrido[3,2-d]pyrimidine-8-carboxamide (G) was reacted with (S)-2-Azetidin-1-yl-1-(3-difluoromethyl-4-fluoro-phenyl)-ethylamine hydrochloride to give the title compound as a white solid. LC/MS [409 (M+H)]; 1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.09 (d, 1H), 9.02 (d, 1H), 8.55 (s, 1H), 8.39 (d, 1H), 8.18 (s, 1H), 7.58 (t, 1H), 7.52 (d, 1H), 7.45 (d, 1H), 7.29 (s, 1H), 7.16 (s, 1H), 7.02 (s, 1H), 5.34 (dd, 1H), 3.20-3.02 (m, 4H), 2.84 (dd, 2H), 1.99-1.85 (m, 2H).
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][N:24]5[CH2:28]CC[CH2:25]5)[CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)=[N:4]1)[CH3:2].[CH2:36]([N:38]=[C:39]=[O:40])[CH3:37]>>[CH3:28][N:24]([CH2:23][C:19]1[CH:18]=[C:17]([C:15]2[NH:14][C:10]3=[N:11][CH:12]=[CH:13][C:8]([C:6]4[C:5]([C:29]5[CH:30]=[CH:31][C:32]([NH:35][C:39]([NH:38][CH2:36][CH3:37])=[O:40])=[CH:33][CH:34]=5)=[N:4][N:3]([CH2:1][CH3:2])[CH:7]=4)=[C:9]3[CH:16]=2)[CH:22]=[CH:21][CH:20]=1)[CH3:25]
Reactant: CCn1cc(-c2ccnc3[nH]c(-c4cccc(CN5CCCC5)c4)cc23)c(-c2ccc(N)cc2)n1
Reactant: CCN=C=O
Product: CCNC(=O)Nc1ccc(-c2nn(CC)cc2-c2ccnc3[nH]c(-c4cccc(CN(C)C)c4)cc23)cc1

Procedure:
Following the procedure described in Example 48 using [4-(1-ethyl-4-{2-[3-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]amine and ethyl isocyanate provided the title compound. ESMS [M+H]+: 534.5
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][CH3:22])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[OH-].[K+].[CH3:25][C@@H:26]([CH2:33][CH3:34])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]Br>C(O)C>[CH3:25][C@@H:26]([CH2:33][CH3:34])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][O:1][C:2]1[CH:7]=[N:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][CH3:22])=[CH:16][CH:15]=3)=[CH:12][CH:13]=2)=[N:4][CH:3]=1
Reactant: CC[C@H](C)CCCCCBr
Reactant: CCCc1ccc(-c2ccc(-c3ncc(O)cn3)cc2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCCc1ccc(-c2ccc(-c3ncc(OCCCCC[C@@H](C)CC)cn3)cc2)cc1
Yield: 62.8 %

Procedure:
5-Hydroxy-2(4'-propyl-biphenyl-4-yl)pyrimidine (10 g, 0.034 mol) was dissolved in ethanol (100 ml), followed by adding KOH (2.1 g, 0.037 mol), refluxing the mixture, dropwise adding (S)-6-methyloctyl bromide (7.7 g, 0.037 mol) over about 15 minutes, further refluxing the mixture for 5 hours, distilling off ethanol (80 ml), dissolving the residue in toluene (100 ml), transferring the solution into a separating funnel, sufficiently washing it with a 2N-NaOH aqueous solution, washing it with water until the washing water became neutral, drying the resulting organic layer over anhydrous magnesium sulfate, distilling off toluene and recrystallizing the residue from ethanol (200 ml) to obtain (S)-5-(6'-methyloctyloxy)-2(4'-propylbiphenyl-4-yl)pyrimidine (8.9 g). This product was a liquid crystal and exhibited the following phase transition points (also see Table 1): ##STR86##
Reaction SMILES: C([C@H](NC(=O)C1C=C(C2C=CC=CC=2)C=C(N2CCCC2=O)C=1)[C@@H](O)C[C@H](C(=O)NCCC(C)(C)C)C)C1C=CC=CC=1.[CH:44]([C@H:47]1[CH2:51][O:50][C:49](=[O:52])[N:48]1[C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[C:56]([OH:58])=O)([CH3:46])[CH3:45].[CH:62]12[CH2:68][CH:65]([CH2:66][CH2:67]1)[CH2:64][CH:63]2[NH:69][C:70](=[O:85])[C@H:71]([CH3:84])[CH2:72][C@H:73]([OH:83])[C@@H:74]([NH2:82])[CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1>>[CH2:75]([C@H:74]([NH:82][C:56](=[O:58])[C:55]1[CH:59]=[CH:60][CH:61]=[C:53]([N:48]2[C@@H:47]([CH:44]([CH3:45])[CH3:46])[CH2:51][O:50][C:49]2=[O:52])[CH:54]=1)[C@@H:73]([OH:83])[CH2:72][C@H:71]([C:70](=[O:85])[NH:69][CH:63]1[CH2:64][CH:65]2[CH2:68][CH:62]1[CH2:67][CH2:66]2)[CH3:84])[C:76]1[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=1
Reactant: C[C@H](C[C@H](O)[C@@H](N)Cc1ccccc1)C(=O)NC1CC2CCC1C2
Reactant: CC(C)[C@H]1COC(=O)N1c1cccc(C(=O)O)c1
Agent: C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)c1cc(-c2ccccc2)cc(N2CCCC2=O)c1)C(=O)NCCC(C)(C)C
Product: CC(C)[C@H]1COC(=O)N1c1cccc(C(=O)N[C@@H](Cc2ccccc2)[C@@H](O)C[C@@H](C)C(=O)NC2CC3CCC2C3)c1

Procedure:
Prepared in an analogous manner to E6 from 3-((S)-4-isopropyl-2-oxo-oxazolidin-3-yl)benzoic acid (D23) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (bicyclo[2.2.1]hept-2-yl)amide (D29).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]=[CH:13][CH:12]1[CH2:17][O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:25](Br)([Br:27])[Br:26]>>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]2[CH:13]([C:25]2([Br:27])[Br:26])[CH:12]1[CH2:17][O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrC(Br)Br
Reactant: O=C(OCc1ccccc1)N1CCC=CC1COC1CCCCO1
Product: O=C(OCc1ccccc1)N1CCC2C(C1COC1CCCCO1)C2(Br)Br

Procedure:
Reaction of 1-benzyloxycarbonyl-2-tetrahydropyranyloxymethyl-1,2,5,6-tetrahydropyridine with bromoform under basic conditions, as in Section XXXVII, gives 3-benzyloxycarbonyl-7,7-dibromo-2-tetrahydropyranyloxymethyl-3-azabicyclo[4.1.0]heptane, which can be further converted into the desired compound by applying methods described in Section XXXVII.
Reaction SMILES: [CH:1]1[N:5]=[CH:4][N:3]2[CH2:6][CH:7]=[C:8]([C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=3)[C:2]=12>CO.[Pd]>[CH:1]1[N:5]=[CH:4][N:3]2[CH2:6][CH2:7][CH:8]([C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=3)[C:2]=12
Reactant: N#Cc1ccc(C2=CCn3cncc32)cc1
Agent: [Pd]
Solvent: CO
Product: N#Cc1ccc(C2CCn3cncc32)cc1

Procedure:
A solution of 0.99 mmol of 4-(5H-pyrrolo[1,2-c]imidazol-7-yl)benzonitrile in 15 ml of MeOH is hydrogenated in the presence of 123 mg of 10% Pd/C at room temperature for 5.5 hours. The reaction mixture is subjected to clarifying filtration and the filtrate is evaporated. From the residue the title compound is obtained by means of flash chromatography (SiO2 60 F) as a pale reddish solid. Rf=0.22 (dichloromethane/ammonia (2M in EtOH) 97:3), Rt=4.43 (Gradient I).
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:18])=[C:10](F)[C:11]=2[O:13][CH:14]([F:16])[F:15])[C:6](=[O:19])[C:5]([C:20]([OH:22])=[O:21])=[CH:4]1)[CH3:2].[CH3:23][CH:24]1[CH2:29][NH:28][CH2:27][CH2:26][NH:25]1>N1C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:18])=[C:10]([N:28]3[CH2:27][CH2:26][NH:25][CH:24]([CH3:23])[CH2:29]3)[C:11]=2[O:13][CH:14]([F:16])[F:15])[C:6](=[O:19])[C:5]([C:20]([OH:22])=[O:21])=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(OC(F)F)c21
Reactant: CC1CNCCN1
Solvent: c1ccncc1
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNC(C)C3)c(OC(F)F)c21
Reaction time: 2 h
Yield: 80.9 %

Procedure:
In 60 ml of pyridine were dissolved 3.19 g (0.01 mole) of 1-ethyl-6,7-difluoro-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 3.0 g (0.03 mole) of 2methylpiperazine, and the mixture was stirred at 105° to 110° C. for 2 hours. Then, the solvent was removed under reduced pressure. Water was added to the residue, and crystals precipitated were collected by filtration, washed with water and ethanol, and dried to obtain 3.23 g of 1-ethyl-6-fluoro-8-difluoromethoxy-7-(3-methylpiperazin-1-Yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid as pale yellow powder.
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].F[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23].O>C(#N)C.C(Cl)Cl>[F:21][C:18]1[CH:19]=[CH:20][C:15]([S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:16]([N+:22]([O-:24])=[O:23])[CH:17]=1
Reactant: O=[N+]([O-])c1cc(F)ccc1F
Reactant: Sc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: ClCCl
Solvent: O
Product: O=[N+]([O-])c1cc(F)ccc1Sc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.3 %

Procedure:
To a mixture of thiophenol (0.96 mL, 9.3 mmol) and potassium carbonate (1.4 g, 10.1 mmol) in 16 mL of dry acetonitrile is added 2,5-difluoronitrobenzene (1.0 mL, 9.2 mmol). The mixture is allowed to stir overnight at rt. Water (30 mL) and CH2Cl2 are added and the layers seperated. The aqueous layer is extracted with CH2Cl2 (3×25 mL). The combined organics are dried over MgSO4, filtered, and concentrated. Recrystallization from EtOAc/heptane gives 2.3 g (99%) of the title compound as a solid, mp 66 67° C.