Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1](C1C=CC=CC=1)([O-])=O.Cl[C:11]1[C:24]2[C:23](=O)[C:22]3[C:17](=[C:18](Cl)[CH:19]=[CH:20][CH:21]=3)[C:16](=[O:27])[C:15]=2[CH:14]=[CH:13][CH:12]=1.NC1C2C(=O)C3C(=CC=CC=3)C(=O)C=2C=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Cu]Cl>[CH:11]1[C:24]2[C:23](=[NH:1])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:27])[C:15]=2[CH:14]=[CH:13][CH:12]=1
Reactant: O=[N+]([O-])c1ccccc1
Reactant: O=C1c2cccc(Cl)c2C(=O)c2cccc(Cl)c21
Agent: Cl[Cu]
Agent: Nc1cccc2c1C(=O)c1ccccc1C2=O
Agent: O=C([O-])[O-]
Product: N=C1c2ccccc2C(=O)c2ccccc21
Temperature: 190 °C
Reaction time: 4 h
Yield: 97 %

Procedure:
A reaction vessel is charged with 5000 parts of nitrobenzene to which are added 428.5 parts of 1,5-dichloroanthraquinone, 670 parts of 1-aminoanthraquinone, 250 parts of anhydrous sodium carbonate and 10 parts of copper(I) chloride. With stirring, the mixture is heated to 190° C. and a further 10 parts of copper(I) chloride are added. After reflux distillation without pressure over 5 hours, the reaction mixture is heated to 240° C. and the pressure rises to 2 bar. Stirring is continued for 4 hours under these conditions. The reaction mixture is cooled and the reaction product is isolated and dried, affording 976 parts (97% yield, based on 1,5-dichloroanthraquinone) of the anthraquinone imide of the formula ##STR2## This anthraquinone imide is converted into a yellow vat dye by a double carbazole cyclisation.
Reaction SMILES: [C:1]([OH:24])(=O)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[NH2:25][C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.C1CCC(N=C=NC2CCCCC2)CC1>>[N:29]1[CH:30]=[CH:31][C:26]([NH:25][C:1](=[O:24])[CH2:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH3:22])=[CH:27][CH:28]=1
Reactant: Nc1ccncc1
Reactant: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(=O)Nc1ccncc1
Yield: 90.6 %

Procedure:
Reaction of docosahexaenoic acid (0.10 g, 0.30 mmol) with 4-aminopyridine (0.03 g, 0.30 mmol) was conducted according to the general amide coupling procedure using DCC to obtain the product as a yellow solid (0.11 g, 91%). EIMS m/z: 405 ([M]+).
Reaction SMILES: O[CH2:2][C:3]1[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]([CH3:10])[N:6]([CH3:9])[C:7]=1[CH3:8].S(Cl)([Cl:18])=O>C1C=CC=CC=1>[Cl:18][CH2:2][C:3]1[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]([CH3:10])[N:6]([CH3:9])[C:7]=1[CH3:8]
Reactant: O=S(Cl)Cl
Reactant: CCOC(=O)c1c(CO)c(C)n(C)c1C
Solvent: c1ccccc1
Product: CCOC(=O)c1c(CCl)c(C)n(C)c1C
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
1.0 g of ethyl 4-(hydroxymethyl)-1,2,5-trimethylpyrrole-3-carboxylate is dissolved in 15 ml of benzene and 0.6 g of thionyl chloride is added dropwise and after total addition the reaction mixture is stirred for 3.5 hours at ambient temperature. The benzene is removed in vacuo leaving the gray solid, ethyl 4-(chloromethyl)-1,2,5-trimethylpyrrole-3-carboxylate.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH2:4]O.S(Cl)(Cl)=O.[CH2:16]([NH:18][CH2:19][CH3:20])[CH3:17]>C(Cl)Cl>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH2:4][N:18]([CH2:19][CH3:20])[CH2:16][CH3:17]
Reactant: COc1ccc(N)c(CO)c1
Reactant: CCNCC
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: CCN(CC)Cc1cc(OC)ccc1N

Procedure:
2-Amino-N,N-diethyl-5-methoxy-benzylamine was prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and diethylamine analogous to Example 1. Proof of structure by IR-, UV- and NMR-spectra. IR-spectrum (methylenechloride):
Reaction SMILES: [F:1][C:2]([F:6])([F:5])[CH2:3][NH2:4].[C:7]([O:11][C:12]([NH:14][C@@H:15]([CH3:28])[C:16]([NH:18][N:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[C:24](OC)=[O:25])=[O:17])=[O:13])([CH3:10])([CH3:9])[CH3:8].C[Al](C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O>[O:17]=[C:16]([NH:18][N:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[C:24](=[O:25])[NH:4][CH2:3][C:2]([F:6])([F:5])[F:1])[C@@H:15]([NH:14][C:12](=[O:13])[O:11][C:7]([CH3:10])([CH3:9])[CH3:8])[CH3:28]
Reactant: NCC(F)(F)F
Reactant: COC(=O)c1cccn1NC(=O)[C@H](C)NC(=O)OC(C)(C)C
Agent: C[Al](C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)Nn1cccc1C(=O)NCC(F)(F)F
Temperature: 80 °C
Reaction time: 8 h

Procedure:
2,2,2-Trifluoroethanamine (680 microl, 8.66 mmols) was added to a solution of (S)-methyl 1-(2-(tert-butoxycarbonylamino)propanamido)-1H-pyrrole-2-carboxylate (900 mg, 2.89 mmols) in toluene (36 ml). A 2M solution of trimethyl aluminium in toluene (7 ml, 14.00 mmols) was added and it was stirred at 80° C. overnight. Water (50 ml) and a 0.5M solution of sodium tartrate (25 ml) were added. It was extracted with ethylacetate. The combined organic layers were washed with water and brine. It was dried, filtered and concentrated in vacuum. The title compound was obtained (1.021 g, 93%).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:45]=[CH:44][C:16]([CH2:17][N:18]([C:31]3[CH:43]=[CH:42][C:34]4[O:35]C(C)(C)[O:37][C:38](=[O:39])[C:33]=4[CH:32]=3)[C:19](=[O:30])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28]C)=[O:27])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>CCO>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:45]=[CH:44][C:16]([CH2:17][N:18]([C:19](=[O:30])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C:31]3[CH:43]=[CH:42][C:34]([OH:35])=[C:33]([CH:32]=3)[C:38]([OH:39])=[O:37])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C#Cc2ccc(CN(C(=O)CCCCCCC(=O)OC)c3ccc4c(c3)C(=O)OC(C)(C)O4)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCc1ccc(C#Cc2ccc(CN(C(=O)CCCCCCC(=O)O)c3ccc(O)c(C(=O)O)c3)cc2)cc1

Procedure:
The titled compound was prepared following the procedure C using methyl 8-[{4-[(4-butylphenyl)ethynyl]benzyl}(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)amino]-8-oxooctanoate and NaOH 1M aq in the presence of EtOH as a white powder (35%). 1H NMR (CDCl3, 300 MHz) δ 10.69 (br s, 1H), 7.57 (d, J=2.3 Hz, 1H), 7.43 (m, 4H), 7.16 (m, 4H), 7.02 (dd, J=8.7, 2.3 Hz, 1H), 6.94 (d, J=8.7 Hz, 1H), 4.87 (s, 2H), 2.62 (t. J=7.5 Hz, 2H), 2.30 (t, J=7.4 Hz, 2H), 2.11 (t, J=7.3 Hz, 2H), 1.60 (m, 6H), 1.36 (m, 2H), 1.25 (m, 4H), 0.93 (t, J=7.3 Hz, 3H). M− (ESI): 554.3, M+ (ESI): 556.4. HPLC, Rt: 5.03 min (Purity: 99%).
Reaction SMILES: [CH3:1][C:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:6])[C:3](=[O:5])[CH3:4].OC1C([O:21][S:22]([C:25]2[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=2)(=[O:24])=[O:23])=C(I)C=CC=1>C(#N)C>[CH3:6][C:2]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)([CH3:1])[C:3](=[O:5])[CH2:4][O:24][S:22]([C:25]1[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=1)(=[O:21])=[O:23]
Reactant: CC(=O)C(C)(C)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Oc2c(O)cccc2I)cc1
Solvent: CC#N
Product: Cc1ccc(S(=O)(=O)OCC(=O)C(C)(C)c2ccccc2)cc1

Procedure:
To a solution of 3-methyl-3-phenyl-butan-2-one (example 207D) (8.7 g, 53.6 mmoles) in ACN (150 mL) is added hydroxy(tosyloxy)iodobenzene (22.1 g, 56.3 mmoles). The reaction mixture is heated at reflux for 5 hours. Solvent and volatiles are removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (heptane:AcOEt) (90:1) to give toluene-4-sulfonic acid 3-methyl-2-oxo-3-phenyl-butyl ester.
Reaction SMILES: CO[CH:3]([O:12]C)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10]Cl)=[CH:6][N:5]=1.[S-2:14].[Na+].[Na+]>O>[CH:3]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][S:14][S:14][CH2:10][C:7]2[CH:8]=[CH:9][C:4]([CH:3]=[O:12])=[N:5][CH:6]=2)=[CH:6][N:5]=1)=[O:12]
Reactant: COC(OC)c1ccc(CCl)cn1
Reactant: [S-2]
Agent: [Na+]
Solvent: O
Product: O=Cc1ccc(CSSCc2ccc(C=O)nc2)cn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 0.1 mole of 2-di(methoxy)methyl-5-chloromethylpyridine in absolute alcohol (150 ml.) is added dropwise at 10°-15° C. over 20 minutes, to a suspension of 6 g. of sodium sulfide (Na2S2) in 50 ml. of absolute alcohol. The mixture stirred at room temperature for 1/2 hour, then 15 min. at 40°-50° C. and poured into 800 ml. of water. The mixture is extracted with ether and the extract is dried over magnesium sulfate and concentrated to an oil. The oil is dissolved in 80 ml. of 1 N hydrochloric acid and heated for 2 min. at 40° C. The mixture is cooled, adjusted to pH 7 with sodium bicarbonate and extracted with ethylacetate. The extract is dried over magnesium sulfate and concentrated to dryness to give bis[2-formyl-5-pyridylmethyl]disulfide
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([N+:10]([O-:12])=[O:11])=[C:4]([O:13][CH3:14])[N:3]=1.[Cl-].[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][Zn+])=[CH:19][CH:18]=1>C1COCC1.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>[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([N+:10]([O-:12])=[O:11])=[C:4]([O:13][CH3:14])[N:3]=2)=[CH:19][CH:18]=1
Reactant: Fc1ccc(C[Zn+])cc1
Reactant: COc1nc(Cl)nc(OC)c1[N+](=O)[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Solvent: C1CCOC1
Product: COc1nc(Cc2ccc(F)cc2)nc(OC)c1[N+](=O)[O-]
Temperature: 25 °C
Yield: 68.2 %

Procedure:
(26) A solution of compound (25) (1.2 g, 5.5 mmol), 4-fluorobenzylzinc chloride (13.1 mL, 0.5 M in THF, 6.6 mmol), tetrakis(triphenylphosphine)palladium (0.13 g, 0.1 mmol) in THF (50 mL) was heated to refluxed for 3 hours under nitrogen. After it cooled to room temperature, the THF was removed in vacuo. The residue was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4. After concentrated, the residue was purified by a column chromatography on silica gel eluting with 5% ethyl acetate in hexane to yield 2-(4-fluoro-benzyl)-4,6-dimethoxy-5-nitro-pyrimidine (26) (1.1 g, 63%). 1H NMR (CDCl3)
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:10]([CH3:12])([CH3:11])[C:9]([CH3:13])=[N:8][C:5]2=[N:6][CH:7]=1.N(C1C=CC=CN=1)N>>[CH3:13][C:9]1[C:10]([CH3:12])([CH3:11])[C:4]2[C:5]([N:8]=1)=[N:6][CH:7]=[CH:2][CH:3]=2
Reactant: CC1=Nc2ncc(Cl)cc2C1(C)C
Agent: NNc1ccccn1
Product: CC1=Nc2ncccc2C1(C)C

Procedure:
Compound 2 is prepared analogously to compound 1 (Example 1), except that 2-hydrazinopyridine is used as a starting material.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.C(OCC)(=O)[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=CC=1C(O)=O>O1CCOCC1.[Cu]I>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1)[CH3:17]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Brc1ccn2ccnc2c1
Agent: [Cu]I
Agent: O=C(O)c1ccccn1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CCOC(=O)Cc1ccn2ccnc2c1
Temperature: 25 °C
Yield: 29 %

Procedure:
To a stirred solution of 7-bromo-imidazo[1,2-a]pyridine (600 mg, 3.0 mmol) and diethyl malonate (0.93 mL, 6.1 mmol) in dry dioxane (15 mL) was added cesium carbonate (3 gm, 9.1 mmol). Argon was bubbled through the mixture for 10 minutes and then copper (I) iodide (116 mg, 0.61 mmol) and picolinic acid (150 mg, 1.22 mmol) were added. The resultant mixture was heated in a sealed tube at 130° C. for 24 hours. The reaction mixture was cooled to room temperature, quenched with water (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×10 mL), brine (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with a gradient of dichloromethane:methanol 100:0 to 98:2 to afford the title compound as an off-white gum in 29% yield, 180 mg.
Reaction SMILES: C(O[C:4]([C:6]1[CH:25]=[CH:24][C:9]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]2)=[CH:8][CH:7]=1)=[O:5])C.C(OC1(O[Si](C)(C)C)CC1)C.[C:37]1(=O)[CH2:40][CH2:39][CH2:38]1>>[CH:17]1([N:14]2[CH2:13][CH2:12][CH:11]([O:10][C:9]3[CH:8]=[CH:7][C:6]([CH:4]=[O:5])=[CH:25][CH:24]=3)[CH2:16][CH2:15]2)[CH2:39][CH2:38][CH2:37][CH2:40]1
Reactant: O=C1CCC1
Reactant: CCOC(=O)c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Agent: CCOC1(O[Si](C)(C)C)CC1
Product: O=Cc1ccc(OC2CCN(C3CCCC3)CC2)cc1

Procedure:
Compounds of Reference Examples 2 and 3 can be produced according to the method of Reference Example 1 but starting from tert-butyl 4-[4-(ethoxycarbonyl)phenoxy]tetrahydro-1(2H)-pyridinecarboxylate and [(1-ethoxycyclopropyl)oxy](trimethyl)silane or cyclobutanone.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:16][OH:17].Cl>N1C=CC=CC=1>[OH:17][N:16]=[CH:13][C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C=O
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C=NO
Temperature: 25 °C
Reaction time: 17 h
Yield: 90.4 %

Procedure:
To a solution of (S)-t-butyl-2-formylpyrrolidine-1-carboxylate (40.94 g) in pyridine (411 mL), hydroxylamine monohydrochloride (28.56 g) was added at 0° C. and the mixture was stirred at room temperature for 17 hours. The reaction mixture was added to a mixture of AcOE (1.5 L) and hydrochloric acid (2 L, 3.0 N). The organic layer was separated, washed with saturated aqueous sodium bicarbonate (1 L), dried (MgSO4), filtered and concentrated to give the titled compound (39.78 g, colorless solid.)
Reaction SMILES: [C:1]1([CH3:22])[CH:6]=[CH:5][C:4]([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)=[CH:11][N:10]=[C:9]([NH:20][CH3:21])[N:8]=2)=[CH:3][CH:2]=1.[C:23]([O:27][C:28](=[O:36])[CH2:29][O:30][CH2:31][CH2:32][CH2:33][CH2:34]Br)([CH3:26])([CH3:25])[CH3:24]>>[C:23]([O:27][C:28](=[O:36])[CH2:29][O:30][CH2:31][CH2:32][CH2:33][CH2:34][N:20]([C:9]1[N:8]=[C:7]([C:4]2[CH:3]=[CH:2][C:1]([CH3:22])=[CH:6][CH:5]=2)[C:12]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[CH:11][N:10]=1)[CH3:21])([CH3:26])([CH3:25])[CH3:24]
Reactant: CNc1ncc(-c2ccc(C)cc2)c(-c2ccc(C)cc2)n1
Reactant: CC(C)(C)OC(=O)COCCCCBr
Product: Cc1ccc(-c2cnc(N(C)CCCCOCC(=O)OC(C)(C)C)nc2-c2ccc(C)cc2)cc1

Procedure:
In the same manner as in Example 22, except that 4,5-di-p-tolyl-2-(methylamino)pyrimidine was used in place of 5,6-diphenyl-2-(methylamino)pyrazine and 2-(4-bromobutyloxy)acetic acid tert-butyl ester was used in place of 2-(4-bromobutyloxy)acetic acid methyl ester, the desired compound was prepared as a pale yellow oily substance.
Reaction SMILES: [CH2:1]([NH:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[CH:19])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C1C=CC=CC=1.[CH2:29]([O:31][C:32](=[O:40])[C:33]1[CH:38]=[CH:37][C:36](I)=[CH:35][CH:34]=1)[CH3:30]>C(N(CC)CC)C.[Cu]I.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>[CH2:1]([NH:8][C:9]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:36]3[CH:37]=[CH:38][C:33]([C:32]([O:31][CH2:29][CH3:30])=[O:40])=[CH:34][CH:35]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: C#Cc1ccc(C2(NCc3ccccc3)CC2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: O=C(O)c1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(C#Cc2ccc(C3(NCc4ccccc4)CC3)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.3 %

Procedure:
Using General Procedure F; benzyl-[1-(4-ethynylphenyl)-cyclopropyl]-amine (Intermediate 127, 65.0 mg, 0.27 mmol) and ethyl-4-iodo benzoate (Reagent A, 68.0 mg, 0.27 mmol) in triethyl amine (8 mL) was treated with copper(I)iodide (16.0 mg, 0.08 mmol) and sparged with argon for 5 minutes. Dichlorobis (triphenylphosphine)palladium(II) (58 mg, 0.08 mmol) was added and the reaction mixture was stirred overnight at room temperature. Column chromatography (2-5% EtOAc-hexanes) afforded 90 mg (90%) of the title compound as an orange solid.
Reaction SMILES: [CH2:1]([N:8]1[CH:11]([C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH2:13])[CH:10]([CH:18]([O:20]C(OCC2C=CC=CC=2)=O)[CH3:19])[C:9]1=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.N1C=CN=C1.[Si:42](Cl)([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43]>CO.[Pd]>[CH2:1]([N:8]1[CH:11]([CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH3:13])[CH:10]([CH:18]([O:20][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[CH3:19])[C:9]1=[O:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C=C(C(=O)OC)C1C(C(C)OC(=O)OCc2ccccc2)C(=O)N1Cc1ccccc1
Agent: [Pd]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CO
Product: COC(=O)C(C)C1C(C(C)O[Si](C)(C)C(C)(C)C)C(=O)N1Cc1ccccc1
Temperature: 0 °C
Yield: 77.5 %

Procedure:
To a solution of 28 mg (0.07 mmol) of 1-benzyl-3-(1-benzyloxycarbonyloxyethyl)-4-(1-methoxycarbonylethenyl)-2-azetidinone dissolved in 2 ml of methanol, 5 mg of 5% palladium charcoal was added and the mixture was stirred under hydrogen atmosphere for a night. The reaction solution was filtered with selite and the filtrate was washed with ethyl acetate and concentrated. To the concentrate were added 1 ml of DMF, 20 mg (0.3 mmol) of imidazole and 45 mg (0.3 mmol) of t-butyldimethylsilylchloride and the mixture was stirred for a night. Ice water was added to the reaction solution and the resultant was extracted with ether, washed with a saturated solution of NaCl, dried with magnesium sulfate, concentrated and purified with 2 g of silica-gel column (hexane:ether 1:1) to give 22 mg of 1-benzyl-4-(1-methoxycarbonylethyl)-3-(1-t-butyldimethylsilyloxyethyl)-2-azetidinone (yield: 84%). Comparison with the NMR data showed α:β=1:1.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[N:5]=[CH:4][N:3]=1.[CH3:16][OH:17]>[Na]>[CH2:12]([N:11]([CH2:14][CH3:15])[C:6]1[C:7]([N+:8]([O-:10])=[O:9])=[C:2]([O:17][CH3:16])[N:3]=[CH:4][N:5]=1)[CH3:13]
Reactant: CCN(CC)c1ncnc(Cl)c1[N+](=O)[O-]
Reactant: CO
Agent: [Na]
Product: CCN(CC)c1ncnc(OC)c1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
In a sulphonation flask are dissolved 17.25 g sodium metal in 1000 ml absolute CH3OH. The reaction mixture is cooled to ambient temperature and then a solution of 116 g 4 -chloro-6-diethylamino-5-nitropyrimidine in 500 ml absolute CH3OH is added dropwise thereto. The reaction temperature rises from 22° to 32°. The reaction mixture is then heated for one hour under reflux. The reaction mixture is cooled and concentrated. The residue is taken up in diethylether, washed with water, the organic phase is partitioned off and dried over Na2SO4, concentrated, chromatographed on a silica gel column (elution with diethylether/hexane 1:10) to give a yellow, clear oil (4-diethylamino-6-methoxy-5-nitropyrimidine), Rf=0.3 in ether/hexane 1:3.
Reaction SMILES: F[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[CH3:11][S-:12].[Na+].Cl>CS(C)=O.C(OCC)(=O)C>[CH3:11][S:12][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1
Reactant: C[S-]
Reactant: O=C(O)c1ccc(F)nc1
Agent: Cl
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CSc1ccc(C(=O)O)cn1
Temperature: 80 °C
Reaction time: 0.25 h

Procedure:
To a solution of 6-fluoronicotinic acid (0.995 g, 7.05 mmol) in 14 mL of dimethylsulfoxide was added sodium thiomethoxide (1.24 g, 17.6 mmol). The mixture was heated 80° C. for 1 hr, cooled to ambient temperature, and treated with concentrated hydrochloric acid (4.5 mL, 0.054 mol). After 15 min, the mixture was diluted with ethyl acetate and concentrated in vacuo to provide 6-(methylthio)nicotinic acid that gave a mass ion (ES+) of 170.1 for [M+H]+.
Reaction SMILES: [CH3:1][C:2](=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[Br:13]Br.O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)(Cl)Cl>[Br:13][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[C:2](=[O:12])[CH3:1]
Reactant: BrBr
Reactant: CCCCCCCCCC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCCCCCC(Br)C(C)=O
Reaction time: 2 h

Procedure:
A solution of undecan-2-one (170 g, 1.0M) in CCl4 (500 ml) was stirred at 20°-25° C. and bromine (160 g) was added over 15 minutes. The solution decolourised rapidly and stirring was continued for 2 hours at 20°-25° C. when water (100 ml) was added. NaHCO3 (92 g) was added portion-wise and the mixture filtered. The filtrate was dried over anhydrous MgSO4 and distilled. The fraction which boiled at 142°-146° C./20 mmHg (116 g) was collected. NMR(CDCl3)=0.7-1.6 (m, 17, C8H17), 2.3 (s, 3, CH3), 4.0-4.4 (t, 1, CH).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].[CH3:31][N:32]1[CH2:37][CH2:36][CH:35]([CH2:38]C2(S([O-])(=O)=O)C=CC(C)=CC2)[CH2:34][C:33]1=[O:50]>CN(C=O)C.CC(C)=O>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:38][CH:35]1[CH2:36][CH2:37][N:32]([CH3:31])[C:33](=[O:50])[CH2:34]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2
Reactant: CC1=CCC(CC2CCN(C)C(=O)C2)(S(=O)(=O)[O-])C=C1
Reactant: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)C(=O)C1
Temperature: 95 °C
Reaction time: 4 h
Yield: 17 %

Procedure:
A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (280 mg, 0.87 mmol), (prepared as described in Example 49), potassium carbonate (370 mg, 2.68 mmol) and 4-(1-methyl-2-oxopiperidin-4-yl)methyl-4-toluene sulphonate (260 mg, 0.87 mmol) in DMF (8 ml) was stirred at 95° C. for 4 hours and allowed to cool to ambient temperature. The reaction mixture was diluted with acetone, filtered and the filtrate evaporated ‘in vacuo’ to give a residue which was purified by column chromatography, eluting with dichloromethane/methanol/0.88 ammonia (100/8/1). The relevant fractions were combined and evaporated ‘in vacuo’ to give an oil which crystallised on trituration with diethyl ether to give 6-methoxy-4-(2-methylindol-5-yloxy)-7-(1-methyl-2-oxopiperidin-4-ylmethoxy)quinazoline (66 mg, 17%).
Reaction SMILES: [N:1]([C@H:4]1[C:29](=[O:30])[N:6]2[CH:7]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[O:18])[C:8](OS(C)(=O)=O)([CH3:11])[CH2:9][S:10][C@H:5]12)=[N+:2]=[N-:3].C1C=CC=CC=1.CCOC(C)=O>CCOC(C)=O>[N:1]([C@H:4]1[C:29](=[O:30])[N:6]2[C:7]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[O:18])=[C:8]([CH3:11])[CH2:9][S:10][C@H:5]12)=[N+:2]=[N-:3]
Reactant: COc1ccc(COC(=O)C2N3C(=O)[C@H](N=[N+]=[N-])[C@H]3SCC2(C)OS(C)(=O)=O)cc1
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: COc1ccc(COC(=O)C2=C(C)CS[C@@H]3[C@@H](N=[N+]=[N-])C(=O)N23)cc1
Temperature: 25 °C
Reaction time: 93 h
Yield: 30.8 %

Procedure:
A mixture of p-methoxybenzyl 7α-azido-3-methanesulfonyloxy-3-methyl-cepham-4-carboxylate (210 mg., 0.46 mMol), EM silica gel 60 (2.5 g.), and 3:1 PhH-EtOAc (5 ml.) is stirred in a capped flask at room temperature for 93 hrs. The mixture is diluted with EtOAc and filtered. The silica gel is washed with more EtOAc. The filtrate and washings are combined, washed with 5% NaHCO3 and brine, dried with MgSO4, filtered, and evaporated in vacuo to a pale yellow oil (158 mg.). The material is purified by plc on a 1000μ × 20 × 20 cm silica gel GF plate using 9:1 PhH-EtOAc as developing solvent. Two major uv visible bands are removed and eluted with EtOAc to yield the products. Band A (Rf 0.47) provides p-methoxybenzyl 7α-azido-3-methyl-ceph-3-em-4-carboxylate (51 mg.) as an oil. Band B (Rf 0.26) yields 6α-azido-2-methyl-2-hydroxymethyl-penam-3-carboxylic acid lactone (27 mg.) as an oil which crystallizes from CHCl3 : mp 164°-166° C. (micro hot stage); ir (Nujol) 4.76, 5.57, 5.67, 7.74, 8.32, and 9.79μ; nmr (100 MHz, DMSO-d6) δ1.59 (s, 3, CH3), 4.30 and 4.52 (ABq, 2, J=10Hz, CH2O), 5.20 (d, l, J=1.8Hz, H5 or H6), 5.28 (s, l, H3) and 5.29 (d, l, J=1.8Hz, H6 or H5); mass spectrum, m/e 240 (M+), 212, and 157.