Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.CO.N1C(C)=CC(C)=CC=1C.C[CH2:22][O:23]CC>O1CCCC1>[CH3:22][O:23][C:6]1[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([Cl:9])[CH:5]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: CCOCC
Solvent: CO
Solvent: Cc1cc(C)nc(C)c1
Solvent: C1CCOC1
Product: COc1cc(Cl)nc(Cl)n1

Procedure:
A solution of 2,4,6-trichloropyrimidine (55 g), methanol (50 ml) and collidine (50 g) is heated in dry tetrahydrofuran (400 ml) for 48 hr. Ether is added and the precipitate is collected. The precipitate is column chromatographed on silica gel to give 6-methoxy-2,4-dichloropyrimidine. This product is mixed with morpholine in THF and stirred at 20-25° to give 6-methoxy-2-morpholino-4-chloropyrimidine. The 6-methoxy-2-morpholino-4-chloropyrimidine is heated with piperazine in pyridine at 60° for 24 hr to give the title compound.
Reaction SMILES: [CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:10]=[C:11]([NH:14][CH:15]=[O:16])[S:12][CH:13]=1)[C:6]([OH:8])=O)[CH3:2].[NH2:17][CH:18]1[C:39](=[O:40])[N:20]2[C:21]([C:36]([OH:38])=[O:37])=[C:22]([CH2:25][S:26][C:27]3[N:31]([CH2:32][C:33]([OH:35])=[O:34])[N:30]=[N:29][N:28]=3)[CH2:23][S:24][C@H:19]12>>[CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:10]=[C:11]([NH:14][CH:15]=[O:16])[S:12][CH:13]=1)[C:6]([NH:17][CH:18]1[C:39](=[O:40])[N:20]2[C:21]([C:36]([OH:38])=[O:37])=[C:22]([CH2:25][S:26][C:27]3[N:31]([CH2:32][C:33]([OH:35])=[O:34])[N:30]=[N:29][N:28]=3)[CH2:23][S:24][C@H:19]12)=[O:8])[CH3:2]
Reactant: CCON=C(C(=O)O)c1csc(NC=O)n1
Reactant: NC1C(=O)N2C(C(=O)O)=C(CSc3nnnn3CC(=O)O)CS[C@H]12
Product: CCON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSc3nnnn3CC(=O)O)CS[C@H]12)c1csc(NC=O)n1
Yield: 54.4 %

Procedure:
2-Ethoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetic acid (syn isomer) (3.0 g.) and 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.12 g.) were reacted according to similar to those of Examples 1(b), 2(b), 3(b) and 6(b) to give 7-[2-ethoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (3.6 g.).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:35])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=2)[N:6]1[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[O:33][CH3:34].[F:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:35])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([F:36])[CH:42]=3)=[CH:18][CH:17]=2)[N:6]1[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[O:33][CH3:34]
Reactant: OB(O)c1cccc(F)c1
Reactant: COC(=O)CC1c2cccc(F)c2N=C(c2ccc(Br)cc2)N1c1cc(C(F)(F)F)ccc1OC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)CC1c2cccc(F)c2N=C(c2ccc(-c3cccc(F)c3)cc2)N1c1cc(C(F)(F)F)ccc1OC

Procedure:
Starting from 100 mg (0.18 mmol) of the bromide from Example 11A, reaction by general method [D] with 30.5 mg (0.22 mmol) of 3-fluorophenylboronic acid, 6.37 mg (0.01 mmol) of bis(triphenylphosphine)palladium(II) chloride and 23.07 mg (0.22 mmol) of sodium carbonate in 10 ml of 1,2-dimethoxyethane and 0.1 ml of water results in 22.6 mg (22% of theory) of the target compound.
Reaction SMILES: Cl[C:2]1[N:6]([CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH3:12])[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C(O)(=O)/C=C/C(O)=O>>[CH2:10]([O:9][CH2:8][CH2:7][N:6]1[C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=[C:2]1[N:21]1[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]1)[CH2:11][CH3:12]
Reactant: CN1CCNCC1
Reactant: CCCOCCn1c(Cl)nc2ccccc21
Agent: O=C(O)/C=C/C(=O)O
Product: CCCOCCn1c(N2CCN(C)CC2)nc2ccccc21

Procedure:
In the same manner as described in Example 1 using 2-chloro-1-[2-(n-propoxy)ethyl]benzimidazole (3.00 g), N-methylpiperazine (3.00 g) and fumaric acid (2.53 g), there are obtained crude crystals, which are recrystallized from ethyl acetate-ethanol to give 1-[2-(n-propoxy)ethyl]-2-(4-methyl-1-piperazinyl)benzimidazole.3/2 fumarate (3.42 g) as colorless prisms, m.p. 165°-166° C.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:22])[CH2:4][CH2:3]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1
Reactant: N#Cc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
Reactant: O=Cc1cc2c(cn1)OCCO2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: N#Cc1ccc2ncc(=O)n(CCN3CCC(NCc4cc5c(cn4)OCCO5)CC3)c2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 49.4 %

Procedure:
To 10 mL of a chloroform solution containing 58 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-cyanoquinoxalin-2(1H)-one and 35 mg of 2,3-dihydro-1,4-dioxino[2,3-c]pyridine-7-carbaldehyde, 11 μL of acetic acid was added, and stirred at room temperature for 1 hour. To the reaction mixture, 67 mg of sodium triacetoxyborohydride was added, and stirred for 2 hours. Aqueous saturated sodium hydrogen carbonate solution was added, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=5:1] to give 43 mg of 1-(2-(4-((2,3-dihydro-1,4-dioxino[2,3-c]pyridin-7-yl)methylamino)piperidin-1-yl)ethyl)-7-cyanoquinoxalin-2(1H)-one as a pale yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][CH:9]=[O:10])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[NH2:12][O:13][CH2:14][CH2:15][CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20].C(N(CC)CC)C>O1CCOCC1>[Cl:1][C:2]1[C:7]([NH:8][CH:9]=[O:10])=[C:6]([NH:12][O:13][CH2:14][CH2:15][CH2:16][P:17]([O:18][CH2:19][CH3:20])([O:21][CH2:22][CH3:23])=[O:24])[N:5]=[CH:4][N:3]=1
Reactant: CCOP(=O)(CCCON)OCC
Reactant: O=CNc1c(Cl)ncnc1Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CCOP(=O)(CCCONc1ncnc(Cl)c1NC=O)OCC
Temperature: 100 °C
Yield: 82.2 %

Procedure:
A mixture of 4,6-dichloro-5-formamidopyrimidine (2.82 g, 14.6 mmol), diethyl 3-(aminooxy)propylphosphonate (3.1 g, 14.6 mmol) and triethylamine (3.1 ml, 22.3 mmol) in dioxan (40 ml) was heated at 100° C. for 4 hours. The solution was cooled to ambient temperature, filtered, and the filtrate evaporated to give a yellow oil. The oil was purified by column chromatography on silica gel (eluting with chloroform: methanol 97:3) to give the title compound as a yellow oil (4.4 g, 74%). 1H NMR: δH (CDCl3) 1.3 (6H, t, J=7Hz, (OCH2CH3)2), 1.6-2.5 (4H, m, CH2CH2P), 3.9-4.5 (6H, m, N--OCH2, (OCH2CH3)2), 7.3-9.3 (3H, broad, --NHCHO, --NH--OCH2).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[CH3:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1>>[CH3:22][N:21]([CH3:23])[C:19](=[O:20])[CH2:18][N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:9]2[S:10][C:5]3[C:4]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:3][C:2]([C:34]4[CH:33]=[N:32][C:31]([CH3:30])=[CH:36][CH:35]=4)=[N:7][C:6]=3[CH:8]=2)[CH2:13][CH2:14]1
Reactant: Cc1ccc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: CN(C)C(=O)CN1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Product: Cc1ccc(-c2nc(N3CCOCC3)c3sc(CN4CCN(CC(=O)N(C)C)CC4)cc3n2)cn1

Procedure:
2-[4-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazin-1-yl]-N,N-dimethyl-acetamide (Example 80) was reacted with 2-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine in General Procedure A. Purification on silica yielded 174. (400 MHz CDCl3): 2.54 (8H, m, CH2), 2.55 (3H, s, CH3), 2.87 (3H, s, CH3), 3.00 (3H, s, CH3), 3.12 (2H, s, CH2), 3.76 (2H, s, CH2), 3.81-3.83 (4H, m, CH2), 3.96-3.99 (4H, m, CH2), 7.16 (1H, m, ar), 7.23 (1H, s, ar), 8.48 (1 h, dd (J=8.06, 2.23), ar), 9.43 (1H, d (J=1.87), ar). MH+496.37
Reaction SMILES: [F:1][C@@:2]12[CH2:12][CH2:11][O:10][C:9]3[CH:13]=[CH:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:8]=3[C@@:7]1([CH3:20])[N:6]=[C:5]([N:21](C(OC(C)(C)C)=O)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:4]([CH3:37])([CH3:36])[S:3]2(=[O:39])=[O:38].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O1CC1>C1COCC1>[F:1][C@@:2]12[CH2:12][CH2:11][O:10][C:9]3[CH:13]=[CH:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:8]=3[C@@:7]1([CH3:20])[N:6]=[C:5]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[C:4]([CH3:37])([CH3:36])[S:3]2(=[O:39])=[O:38]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=N[C@]2(C)c3cc([N+](=O)[O-])ccc3OCC[C@@]2(F)S(=O)(=O)C1(C)C
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CO1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC1=N[C@]2(C)c3cc([N+](=O)[O-])ccc3OCC[C@@]2(F)S(=O)(=O)C1(C)C
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 40.2 %

Procedure:
To an oven dried flask was added tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (See procedure for Intermediate 24, Step 1) (0.260 g, 0.475 mmol) and THF (3.17 mL). The resulting mixture was cooled to −78° C. and LHMDS (1 M in THF; 0.712 mL, 0.712 mmol) was added and the mixture was stirred for 40 minutes and then oxirane (7.91 mL, 9.50 mmol) was added. The dry ice/acetone bath was removed and the mixture was stirred for 30 minutes. The resulting mixture was treated with saturated aqueous ammonium chloride and extracted with EtOAc. The organic layer was concentrated and the crude material was eluted through a silica gel column using 10-50% EtOAc/Heptane. The desired fractions were combined and concentrated down to yield tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (0.090 g, 0.191 mmol, 40.2% yield)). ESI MS: 494.1 [M+Na] and a mixture of tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate and tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (89 mg, 0.156 mmol, 32.8% yield) ESI MS: 494.1/594.1 [M+Na].
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([NH2:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])[CH2:10][CH2:9]1)=O)(C)(C)C.[F:23][CH:24]([F:38])[O:25][C:26]1[CH:27]=[CH:28][C:29]([O:36][CH3:37])=[C:30]([S:32]([Cl:35])(=[O:34])=[O:33])[CH:31]=1>>[ClH:35].[F:38][CH:24]([F:23])[O:25][C:26]1[CH:27]=[CH:28][C:29]([O:36][CH3:37])=[C:30]([S:32]([NH:20][C:18]2[CH:17]=[CH:16][C:15]([O:21][CH3:22])=[C:14]([N:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:19]=2)(=[O:34])=[O:33])[CH:31]=1
Reactant: COc1ccc(OC(F)F)cc1S(=O)(=O)Cl
Reactant: COc1ccc(N)cc1N1CCN(C(=O)OC(C)(C)C)CC1
Product: COc1ccc(NS(=O)(=O)c2cc(OC(F)F)ccc2OC)cc1N1CCNCC1
Product: Cl

Procedure:
The compound was prepared as described for Example 1 by reaction of 4-(5-amino-2-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester with commercially available 5-difluoromethoxy-2-methoxybenzenesulfonylchloride followed by deprotection under acidic conditions.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=1.O1CCOCC1.[CH3:18][C:19]1([CH3:26])[C:23]([CH3:25])([CH3:24])[O:22][BH:21][O:20]1.C(N(CC)CC)C>C(OCC)(=O)C>[CH3:18][C:19]1([CH3:26])[C:23]([CH3:25])([CH3:24])[O:22][B:21]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=2)[O:20]1
Reactant: CC(C)Oc1ccc(Br)cc1
Reactant: CC1(C)OBOC1(C)C
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)Oc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 47 %

Procedure:
1-Bromo-4-isopropoxybenzene was combined with dioxane (10.5 mL) and dichloropalladium(dppf) dichloromethane complex (36 mg) under argon. 4,4,5,5-Tetramethyl-1,3,2-dioxaborolane (0.96 mL) was added followed by triethylamine (1.29 mL). The reaction was heated to 90° C. for 23 hours after which, dichloropalladium(dppf) dichloromethane complex (36 mg), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.96 mL) and triethylamine (1.29 mL) was added. Heating was continued for an additional 19 hours after which, it was cooled to room temperature and diluted with ethyl acetate (25 mL). The mixture was washed with water (2×20 mL) and brine (20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. Purification of the residue on silica gel (0% to 50% ethyl acetate/hexane over 40 minutes) gave 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isopropoxybenzene (544 mg). Yield=47%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH2:10][N:11]1[N:15]=[N:14][CH:13]=[N:12]1.[CH:17](Br)([CH3:19])[CH3:18]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([O:16][CH:17]([CH3:19])[CH3:18])=[CH:10][N:11]1[N:15]=[N:14][CH:13]=[N:12]1
Reactant: CC(C)Br
Reactant: O=C(Cn1ncnn1)c1ccc(Cl)cc1Cl
Product: CC(C)OC(=Cn1ncnn1)c1ccc(Cl)cc1Cl

Procedure:
Analogously to Example 7a,b, after reacting 1-(2,4-dichlorophenyl)-2-tetrazol-2-yl-ethanone with isopropyl bromide there was obtained 2-[2-(2,4-dichloro-phenyl)-2-isopropoxy-vinyl]-2H-tetrazole as a colourless oil. [M]+ =299.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([CH3:19])=[N:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[N:10][CH:11]=1)=[O:5])C.[OH-].[Na+].C1COCC1.CO>O>[F:18][C:14]1[CH:13]=[C:12]([C:9]2[N:8]=[C:7]([CH3:19])[C:6]([C:4]([OH:5])=[O:3])=[CH:11][N:10]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(=O)c1cnc(-c2cccc(F)c2)nc1C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: Cc1nc(-c2cccc(F)c2)ncc1C(=O)O
Yield: 85.5 %

Procedure:
A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid ethyl ester (6.7 g, 27.2 mmol) and NaOH (2.1 g, 54.4 mmol) in a 1:1:1 solution of THF, MeOH and water (300 mL) is heated at reflux for 45 min. The THF/MeOH is evaporated, and the aqueous solution is treated with 3 N HCl to adjust the pH to between 2 and 3. The solid is filtered off, washed with water and dried in vacuo to yield 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5.4 g, 91%) as a solid. MS: 233 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.85 (s, 3H), 7.24 (m, 1H), 7.50 (m, 1H), 8.17 (m, 1H), 8.32 (m, 1H), 9.20 (s, 1H).
Reaction SMILES: C=CC1C=CC=CC=1.[CH2:9]([O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19]CCO)[CH2:10]CC.[NH2-].[Na+]>C1COCC1>[CH2:9]([O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][OH:19])[CH3:10]
Reactant: CCCCOCCOCCOCCO
Agent: [NH2-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: C=Cc1ccccc1
Product: CCOCCOCCO
Yield: 50 %

Procedure:
Polymerization of styrene with the system NaNH2 and triethylene glycol monobutyl ether. Polymerization is allowed to proceed from 8.32 g (8·10-22 mole) of styrene in in 30 cc THF in the presence of 0.98 g (25·10-3 mole) of sodium amide and 1.71 g (8.3·10-3 mole) of triethylene glycol monobutyl ether. The reaction mixture which is obtained prior to the addition of the monomer has a yellow color which is more pronounced than that obtained with diethylene glycol monoethyl ether, contrary to the results which have been obtained with glycol monomethyl ether. At the end of four hours, a polymer is obtained in 50% yield, with Mn=8500.
Reaction SMILES: CON(C)[C:4]([C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[O:24][CH3:25])[CH:14]=[CH:15][CH:16]=2)[CH:10]=1)=[O:5].[S:27]1[CH:31]=[CH:30][N:29]=[CH:28]1>>[F:23][C:19]1[C:18]([O:24][CH3:25])=[C:17]([C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([N:9]3[CH:10]=[C:6]([C:4]([C:28]4[S:27][CH:31]=[CH:30][N:29]=4)=[O:5])[N:7]=[CH:8]3)[CH:12]=2)[CH:22]=[CH:21][CH:20]=1
Reactant: c1cscn1
Reactant: COc1c(F)cccc1-c1cccc(-n2cnc(C(=O)N(C)OC)c2)c1
Product: COc1c(F)cccc1-c1cccc(-n2cnc(C(=O)c3nccs3)c2)c1

Procedure:
This compound is prepared by method C using compound 12h and thiazole
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[C:13]2[C:8](=[C:9]([O:16]C)[C:10]([O:14]C)=[CH:11][CH:12]=2)[CH2:7][CH:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:5]=1.B(Cl)(Cl)[Cl:25].CO>ClCCCl>[ClH:25].[NH2:2][CH2:3][C:4]1[C:13]2[C:8](=[C:9]([OH:16])[C:10]([OH:14])=[CH:11][CH:12]=2)[CH2:7][CH:6]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:5]=1
Reactant: ClB(Cl)Cl
Reactant: COc1ccc2c(c1OC)CC(c1ccccc1)C=C2CN
Agent: Cl
Solvent: ClCCCl
Solvent: CO
Product: NCC1=CC(c2ccccc2)Cc2c1ccc(O)c2O
Temperature: 25 °C
Reaction time: 18 h
Yield: 56 %

Procedure:
A slurry of 10 g (25 mmol) of 1-aminomethyl-5,6-dimethoxy-3-phenyl-3,4-dihydronaphthalene hydrochloride, from Step 2, in 150 mL of 1,2-dichloroethane was cooled to 10° C. under a nitrogen atmosphere. Boron trichloride was passed through the reaction mixture until 27 g (230 mmol) had been added. The reaction mixture was allowed to warm to ambient temperature and stirred for 18 h. The reaction mixture was then cooled in ice and 100 mL of methanol was added dropwise. The reaction mixture was again allowed to warm to ambient temperature and concentrated in vacuo. Twice, 500 mL portions of methanol were added to the residue and it was reconcentrated. The resultant foam was dissolved in 40 mL of ethanol, filtered and the solution was treated with 40 mL of methylene chloride and 80 mL of heptane. Off- white crystals of 1-aminomethyl-5,6-dihydroxy-3-phenyl-3,4-dihydronaphthalene hydrochloride (5.1 g, 56% yield) were collected by filtration, m.p. 204°-205° C. The 1H NMR spectrum was identical to the spectrum for the product of Example 2A.
Reaction SMILES: [CH3:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[CH:25]=[CH2:26]>C(#N)C>[CH2:26]([N:15]1[CH2:16][CH2:17][CH:12]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])[C:2]=2[CH3:1])[CH2:13][CH2:14]1)[CH:25]=[CH2:24]
Reactant: C=CCBr
Reactant: Cc1c(C2CCNCC2)cccc1S(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: C=CCN1CCC(c2cccc(S(C)(=O)=O)c2C)CC1

Procedure:
Preparation according to Example 1: 4-[2-methyl-3-(methylsulfonyl)phenyl]piperidine (0.01 g), acetonitrile (2 ml), potassium carbonate (0.01) and allylbromide (0.01 g). MS m/z (rel. intensity, 70 eV) 293 (M+, 16), 292 (16), 278 (26), 266 (bp), 129 (19).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][CH:20]=2)=[CH:14][CH:13]=1)=S.C1([N:39]=[C:40]=[N:41]C2CCCCC2)CCCCC1.C(N(C(C)C)CC)(C)C.N#CN>C(Cl)Cl.C1COCC1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][CH:20]=2)=[CH:14][CH:13]=1)=[N:41][C:40]#[N:39]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: COc1cc2nccc(Oc3ccc(NC(=S)Nc4ccccc4C)cc3)c2cc1OC
Agent: N#CN
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: ClCCl
Product: COc1cc2nccc(Oc3ccc(NC(=NC#N)Nc4ccccc4C)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.7 %

Procedure:
N-(2-Methylphenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea (24 mg) obtained in Example 170, dicyclohexylcarbodiimide (45 mg) and a catalytic amount of diisopropylethyl amine were dissolved in methylene chloride (7 ml), to which a solution of cyanamide (28 mg) in THF (1 ml) was added, and the admixture was stirred at room temperature overnight. After removing the solvent by distillation, the resulting residue was purified by column chromatography on silica gel eluting with chloroform/methanol (100/1) to obtain 18 mg of the title compound (yield: 76%).
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH:20]=[CH2:21])[C@H:10]([CH2:22][OH:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].N1C=CN=C1>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([C@@H:8]1[N:12]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:11]([CH:20]=[CH2:21])[C@H:10]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=C[C@H]1[C@H](CO)C[C@H](C(=O)OC(C)(C)C)N1Cc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=C[C@H]1[C@H](CO[Si](C)(C)C(C)(C)C)C[C@H](C(=O)OC(C)(C)C)N1Cc1ccccc1

Procedure:
A solution of (±)-(2S,3R,5R)-1-benzyl-2-vinyl-3-(hydroxymethyl)-pyrrolidine-5-carboxylic acid t-butyl ester (3.6 g, 11.4 mmole), tert-butyldimethylsilyl chloride (3.7 g, 24.5 mmole) and imidazole (2.8 g, 41.2 mmole) in 60 mL of DMF was stirred at room temperature for 1.5 hours. The reaction was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% ethyl acetate/hexanes to provide the title compound, as a colorless oil (yield: 3.5 g, 71%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][C:10](=[O:14])[O:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:24]=1[C:25](Cl)=[O:26]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12](=[O:13])[N:11]([C:25](=[O:26])[C:24]3[C:23]([F:22])=[CH:31][CH:30]=[CH:29][C:28]=3[F:32])[C:10](=[O:14])[O:9]2)=[CH:6][CH:7]=1
Reactant: O=C(Cl)c1c(F)cccc1F
Reactant: O=c1[nH]c(=O)n(-c2ccc(F)cc2)o1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(c1c(F)cccc1F)n1c(=O)on(-c2ccc(F)cc2)c1=O
Reaction time: 24 h

Procedure:
2-(4-Fluorophenyl)-1,2,4-oxadiazolidin-3,5-dione (0.03 mole), toluene (100 ml) and triethylamine (5 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. 2,6-Difluorobenzoyl chloride (0.03 mole) dissolved in toluene (20 ml) is then added to the reaction flask and the resulting mixture is heated at reflux with stirring for a period of about 24 hours. After this time the reaction mixture is filtered and the filtrate is washed with water, dilute hydrochloric acid and with aqueous sodium bicarbonate. The washed solution is then dried over anhydrous magnesium sulfate. The dried solution is stripped of solvent under reduced pressure leaving a solid residue. The residue is recrystallized to yield the desired product 2-(4-fluorophenyl)-4-(2,6-difluorobenzoyl)-1,2,4-oxadiazolidin-3,5-dione.