Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:11]([CH2:14][C:15]3[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=3[C:17]#[N:18])(=[O:13])=[O:12])[CH:8]=2)[NH:3]1.[CH3:23][C:24]1[C:28]([C:29]([N:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[O:30])=[C:27]([CH3:38])[NH:26][C:25]=1[CH:39]=O.N1CCCCC1>C(O)C>[CH3:23][C:24]1[C:28]([C:29]([N:31]2[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]2)=[O:30])=[C:27]([CH3:38])[NH:26][C:25]=1/[CH:39]=[C:10]1\[C:2](=[O:1])[NH:3][C:4]2[C:9]\1=[CH:8][C:7]([S:11]([CH2:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[C:17]#[N:18])(=[O:12])=[O:13])=[CH:6][CH:5]=2
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)N1CCN(C)CC1
Reactant: N#Cc1ccccc1CS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4ccccc4C#N)cc32)c(C)c1C(=O)N1CCN(C)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 70.7 %

Procedure:
To a solution of 2-(2-oxo-2,3-dihydro-1H-indole-5-sulfonylmethyl)-benzonitrile (100 mg, 0.32 mmol) and 3,5-dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (79 mg, 0.32 mmol) in ethanol (4 mL) was added piperidine (0.1 mL). The reaction mixture was stirred at 25° C. for three days. The solvent was evaporated and the residue was purified on a silica gel column eluting with MeOH—CH2Cl2 10:90 to provide 123 mg (71%) of 2-{3-[1-[3,5-dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrol-2-yl]-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonylmethyl}-benzonitrile as a pale orange solid.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[O:12][N:11]=[C:10]([CH3:13])[C:9]=1[C:14]([O:16]C)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:18]>O>[C:1]([NH:5][C:6]([C:8]1[O:12][N:11]=[C:10]([CH3:13])[C:9]=1[C:14]([NH2:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1c(C)noc1C(=O)NC(C)(C)C
Reactant: N
Solvent: O
Product: Cc1noc(C(=O)NC(C)(C)C)c1C(N)=O

Procedure:
4.0 g of methyl 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylate and 50 ml of concentrated ammonia are refluxed for 3 hours. After cooling, the mixture is diluted with water and extracted with dichloromethane and the organic phase is evaporated down. 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxamide is obtained as colorless crystals of melting point 155°-158° C. (compound No. 1).
Reaction SMILES: [C:1]([N:8]([C:13]12[CH2:22][C:17]3([CH3:23])[CH2:18][CH:19]([CH2:21][C:15]([CH3:24])([CH2:16]3)[CH2:14]1)[CH2:20]2)[CH2:9][C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[O-:25][Mn](=O)(=O)=O.[K+].Cl>[OH-].[K+].O.CCOC(C)=O>[C:1]([N:8]([C:13]12[CH2:14][C:15]3([CH3:24])[CH2:16][C:17]([CH3:23])([CH2:18][C:19]([OH:25])([CH2:21]3)[CH2:20]1)[CH2:22]2)[CH2:9][C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC12CC3CC(C)(C1)CC(N(CC(=O)O)C(=O)OC(C)(C)C)(C3)C2
Reactant: O=[Mn](=O)(=O)[O-]
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Product: CC12CC3(C)CC(O)(C1)CC(N(CC(=O)O)C(=O)OC(C)(C)C)(C2)C3
Temperature: 90 °C
Yield: 102 %

Procedure:
To a solution of N-BOC-(3,5-dimethyladamantan-1-yl)-glycine (1.79 g, 5.3 mmol) in 2% KOH/water (75 mL) at rt was added KMnO4 (1.0 g, 6.3 mmol). The reaction was heated to 90° C. for 2 h. An additional portion of KMnO4 (0.3 g, 1.9 mmol) was added and the reaction was heated at 90° C. for an additional 1.5 h. The reaction was then diluted with EtOAc (150 mL) and with vigorous mixing the pH was addjusted to ˜3 with 1N HCl. The EtOAc layer was separated and set aside. The aqueous layer was then extracted once more with EtOAc and twice with dichloromethane. The combined organics were dried over MgSO4, filtered and concentrated to give N-BOC-(3-hydroxy-5,7-dimethyladamant-1-yl)-glycine (1.91 g). MS m/e (M+H)+=354.2
Reaction SMILES: [C:1](O)(=O)[CH3:2].[NH2:5][C:6]1[C:14]([NH2:15])=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9]>Cl>[CH3:1][C:2]1[NH:5][C:6]2[C:7]([C:8]([OH:10])=[O:9])=[CH:11][CH:12]=[CH:13][C:14]=2[N:15]=1
Reactant: Nc1cccc(C(=O)O)c1N
Reactant: CC(=O)O
Agent: Cl
Product: Cc1nc2cccc(C(=O)O)c2[nH]1
Yield: 72 %

Procedure:
Acetic acid (0.23 ml) was added to a solution of 2,3-diaminobenzoic acid (200 mg, 1.32 mmol) in hydrochloric acid (4M, 3.2 ml) and the mixture was refluxed for 1 hour. Solvents were evaporated and the residual solid was redissolved in boiling methanol (5 ml) and decolorised with activated charcoal. Removal of the solvent furnished 2-methylbenzimidazole-4-carboxylic acid as an amorphous white solid (167.5 mg, 72%); δH (d6 -DMSO) 2.9 (3H, s, imidazole-2-CH3), 7.6-7.8 (1H, t, Ar-5H) 8.1 (2H, d, Ar-4/6H); m/z (EI 176 (M+), 158, 130.
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:25](=[O:26])[N:6]2[C@@H:7]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)=[O:13])[C:8](=O)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[Cl:27][C:28]1[N:35]2[C:31]([S:32][C:33]([Sn](CCCC)(CCCC)CCCC)=[CH:34]2)=[C:30]([C:49]([C:51]2[CH:52]=[N:53][CH:54]=[CH:55][CH:56]=2)=[O:50])[N:29]=1>>[Cl:27][C:28]1[N:35]2[C:31]([S:32][C:33]([C:8]3[C@H:9]([CH3:10])[C@@H:5]4[C@@H:4]([C@H:2]([OH:1])[CH3:3])[C:25](=[O:26])[N:6]4[C:7]=3[C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=3)=[O:13])=[CH:34]2)=[C:30]([C:49]([C:51]2[CH:52]=[N:53][CH:54]=[CH:55][CH:56]=2)=[O:50])[N:29]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn2c(Cl)nc(C(=O)c3cccnc3)c2s1
Reactant: C[C@@H](O)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4c(Cl)nc(C(=O)c5cccnc5)c4s3)[C@H](C)[C@H]12
Yield: 89.5 %

Procedure:
4-Nitrobenzyl (1S,5R,6S)-2-[5-chloro-7-(pyridin-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (712 mg) was prepared in the same manner as in step a) of Example 1, except that 474 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 730 mg of 5-chloro-7-(pyridin-3-yl)carbonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole were used as the starting compounds.
Reaction SMILES: Cl.[NH2:2][C@@H:3]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)=[O:5].[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21]1[C:29](O)=[O:30]>>[CH2:13]([C@H:3]([NH:2][C:29]([C:21]1[NH:20][C:28]2[C:23]([CH:22]=1)=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:30])[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)=[O:5])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C(O)c1cc2ccccc2[nH]1
Reactant: N[C@@H](Cc1ccccc1)C(=O)N1CCC(O)CC1
Agent: Cl
Product: O=C(N[C@@H](Cc1ccccc1)C(=O)N1CCC(O)CC1)c1cc2ccccc2[nH]1

Procedure:
(S)-2-Amino-1-(4-hydroxy-piperdin-1-yl)-3-phenyl-propan-1-one hydrochloride (3.4 mmol) and 1H-indole-2-carboxylic acid (3.7 mmol) were coupled according to Procedure A (0-25° C. reaction temperature, 48 hour reaction time). The product was purified by chromatography on silica gel eluted with 50, 75 and 100% ethyl acetate in hexanes, followed by trituration with 1:1 ether-hexanes. Yield 1.14 g, 88%; HPLC (60/40) 3.52 minutes (98%); PBMS 392 (MH+, 100%);
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[S:11](=[O:14])(=[O:13])[NH2:12].[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]1[CH3:25].[Cl-].[Al+3].[Cl-].[Cl-].C(O)(C)C>ClC(Cl)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:16]([CH3:15])[C:17]=2[CH3:25])=[O:7])=[CH:4][C:3]=1[S:11](=[O:14])(=[O:13])[NH2:12]
Reactant: NS(=O)(=O)c1cc(C(=O)Cl)ccc1Cl
Reactant: Cc1cc2ccccc2n1C
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(C)O
Solvent: CC(Cl)Cl
Product: Cc1c(C(=O)c2ccc(Cl)c(S(N)(=O)=O)c2)c2ccccc2n1C

Procedure:
is obtained as described in Example 10 (a) from 10 g 4-chloro-3-sulfamoylbenzoyl chloride and 6.53 g 1,2-dimethylindole in dichloro-ethane in the presence of 12 g aluminum chloride. After treatment with isopropanol, crystals having a melting point of 247°-249° C. are obtained.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:16])[N:9]2[CH2:12][C:13]([OH:15])=O)=[CH:4][C:3]=1[C:17]([F:20])([F:19])[F:18].[Br:21][C:22]1[C:23]([C:28]2[NH:32][N:31]=[CH:30][N:29]=2)=[C:24]([NH2:27])[S:25][CH:26]=1>>[Br:21][C:22]1[C:23]([C:28]2[NH:32][N:31]=[CH:30][N:29]=2)=[C:24]([NH:27][C:13](=[O:15])[CH2:12][N:9]2[C:10]3[C:5](=[CH:4][C:3]([C:17]([F:19])([F:18])[F:20])=[C:2]([F:1])[CH:11]=3)[CH:6]=[CH:7][C:8]2=[O:16])[S:25][CH:26]=1
Reactant: Nc1scc(Br)c1-c1ncn[nH]1
Reactant: O=C(O)Cn1c(=O)ccc2cc(C(F)(F)F)c(F)cc21
Product: O=C(Cn1c(=O)ccc2cc(C(F)(F)F)c(F)cc21)Nc1scc(Br)c1-c1ncn[nH]1

Procedure:
N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide was synthesized from 2-(7-fluoro-2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetic acid and 4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-amine according to protocol A. Retention time (min)=6.276, method [7], MS (ESI) 516.0 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 8.54 (b s, 1H), 8.37 (d, J=8.24 Hz, 1H), 8.20 (d, J=9.34 Hz, 1H), 7.89 (d, J=13.72 Hz, 1H), 7.31 (s, 1H), 6.81 (d, J=9.34 Hz, 1H), 5.28 (s, 2H).
Reaction SMILES: C([N:3]([C:31](=O)[C:32]1[CH:37]=[CH:36][C:35](O)=[CH:34]C=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[CH:14]1[CH2:23][CH2:22][C:21]2[CH:20]=[C:19]([O:24]C(=O)C(C)(C)C)[CH:18]=[CH:17][C:16]=2[CH2:15]1)C.[N:40]1([C:48](=O)[CH2:49]Cl)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>>[N:40]1([CH2:48][CH2:49][O:10][C:8]2[CH:7]=[CH:6][C:36]([CH2:37][CH2:32][CH2:31][NH:3][C:4]3[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=3[CH:14]3[CH2:23][CH2:22][C:21]4[CH:20]=[C:19]([OH:24])[CH:18]=[CH:17][C:16]=4[CH2:15]3)=[CH:35][CH:34]=2)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1
Reactant: O=C(CCl)N1CCCCCCC1
Reactant: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)c(OC)cc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Product: COc1cc(NCCCc2ccc(OCCN3CCCCCCC3)cc2)c(C2CCc3cc(O)ccc3C2)cc1OC
Yield: 11.7 %

Procedure:
Synthesized from pivalic acid 6-{2-[ethyl(4-hydroxybenzoyl)amino]-4,5-dimethoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (19 mg) and 1-azocan-1-yl-2-chloroethanone (13 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (1.2 mg) was obtained.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[NH2:16][C:17]1[C:25]([Cl:26])=[CH:24][C:20]([C:21](O)=[O:22])=[C:19]([O:27][CH3:28])[CH:18]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[NH2:16][C:17]1[C:25]([Cl:26])=[CH:24][C:20]([C:21]([NH:1][CH2:2][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)=[O:22])=[C:19]([O:27][CH3:28])[CH:18]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Reactant: CC(C)(C)OC(=O)N1CCC(CN)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 102.4 %

Procedure:
4-Aminomethyl-1-tert-butoxycarbonylpiperidine (10.0 g) was dissolved in dimethylformamide and 4-amino-5-chloro-2-methoxybenzoic acid (9.4 g) and 1-hydroxybenzotriazole (6.6 g) were added. After stirring at 0° C. for 40 min, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (9.4 g) was added, and the mixture was stirred at room temperature for 24 hr. The reaction mixture was concentrated under reduced pressure. Aqueous potassium carbonate solution was added to the residue and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give 19.0 g of 4-amino-5-chloro-N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)-2-methoxybenzamide.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[CH:17]=[CH:16][C:15]([S:18]([NH:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:20])=[O:19])=[CH:14][CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([NH:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])(=[O:19])=[O:20])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1ccc(Br)cc1
Reactant: OB(O)c1ccc(O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1ccc(-c2ccc(O)cc2)cc1
Yield: 65.3 %

Procedure:
1,1-Dimethylethyl (2-{[(4′-hydroxy-4-biphenylyl)sulfonyl]amino}ethyl)carbamate (246 mg, 65%) was prepared as an off-white solid from (4-hydroxyphenyl)boronic acid (132 mg, 0.96 mmol), 1,1-dimethylethyl (2-{[(4-bromophenyl)sulfonyl]amino}ethyl)carbamate (362 mg, 0.96 mmol), Pd(PPh3)2Cl2 (100 mg, 0.14 mmol), 2M Na2CO3 (2 mL) and DME (4 mL) in a manner similar to Example 21, Step 3, and worked up in a manner similar to Example 9, Step 3. 1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.75 (s, 4H), 7.61 (t, 1H, J=5.9 Hz), 7.54 (d, 2H, J=8.6 Hz), 6.84 (d, 2H, J=8.6 Hz), 6.76 (t, 1H, J=5.6 Hz), 2.97-2.89 (m, 2H), 2.76-2.68 (m, 2H), 1.30 (s, 9H); LRMS (ESI), m/z 391 (M−H).
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[N:10]1[N:11]([CH2:15][C:16]2[CH:25]=[CH:24][C:19]([O:20][CH2:21][CH2:22]Br)=[CH:18][CH:17]=2)[N:12]=[CH:13][CH:14]=1>CN(C)C=O>[N:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[O:3][CH2:22][CH2:21][O:20][C:19]1[CH:24]=[CH:25][C:16]([CH2:15][N:11]2[N:12]=[CH:13][CH:14]=[N:10]2)=[CH:17][CH:18]=1
Reactant: Oc1ccccn1
Reactant: BrCCOc1ccc(Cn2nccn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(OCCOc2ccc(Cn3nccn3)cc2)nc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a mixture of 5 ml of anhydrous N,N-dimethylformamide and 51 mg of sodium hydride (60% oil dispersion) is added dropwise an anhydrous N,N-dimethylformamide (3 ml) solution of 121 mg of 2-hydroxypyridine under stirring over 10 minutes. After stirring at room temperature for 1 hour, the mixture is cooled to 5° to 10° C., to which an anhydrous N,N-dirmethylformamide (2 ml) solution of 300 mg of 2-[4-(2-2H-1,2,3-triazolyl)methylphenoxy]ethyl bromide is added dropwise over 30 minutes. The mixture is then stirred at room temperature overnight. The reaction mixture is poured into 50 ml of ice water, which is extracted with twice with 30 ml of toluene. The organic layers are combined, washed with water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is subjected to silica gel column chromatography, which affords 4-(2-2H-1,2,3-triazolyl)methylphenyl 2-(2-pyridyloxy)ethyl ether.
Reaction SMILES: [CH3:1]I.C(=O)([O-])[O-].[K+].[K+].[Cl:9][C:10]1[CH:11]=[C:12]2[S:18][C:17]([SH:19])=[N:16][C:13]2=[N:14][CH:15]=1.O>CN(C)C=O>[Cl:9][C:10]1[CH:11]=[C:12]2[S:18][C:17]([S:19][CH3:1])=[N:16][C:13]2=[N:14][CH:15]=1
Reactant: Sc1nc2ncc(Cl)cc2s1
Reactant: CI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CSc1nc2ncc(Cl)cc2s1
Temperature: 25 °C
Reaction time: 68 h
Yield: 81.5 %

Procedure:
328 g (2.31 mol) of methyl iodide were added dropwise to a stirred suspension of 363 g (2.62 mol) of potassium carbonate and 354 g (1.75 mol) of 6-chloro-2-mercaptothiazolo[4,5-b]pyridine from Example 1.2 in 2.28 l of dimethylformamide at 5° C. The reaction mixture was stirred at ambient temperature for 68 h and then poured into 4.5 l of demineralized water. The precipitate was filtered, rinsed with water (2×500 ml) and then dried in vacuo at 45° C. to give 308.9 g (yield: 81%) of 6-chloro-2-(methylthio)thiazolo[4,5-b]pyridine.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].Br[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20]>>[OH:12][C:5]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=2)[NH:7][C:6]1=[O:11]
Reactant: Cc1ccccc1Br
Reactant: O=C1Nc2ccc(I)cc2C1=O
Product: Cc1ccccc1C1(O)C(=O)Nc2ccc(I)cc21

Procedure:
With 5.46 g of 5-iodoisatin and 1-bromo-2-methyl benzene as starting materials, 5.87 g of the title compound (brown solid) was obtained by a similar method to Step 21-1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH2:14][C:15](=[O:18])[NH:16][N:17]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(O[CH:24](N(C)C)[N:25]([CH3:27])[CH3:26])(C)(C)C>C(#N)C>[CH3:24][N:25]([CH:27]=[C:14]1[C:13]([C:5]2[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:17][NH:16][C:15]1=[O:18])[CH3:26]
Reactant: COc1cc(C2=NNC(=O)C2)cc(OC)c1OC
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Solvent: CC#N
Product: COc1cc(C2=NNC(=O)C2=CN(C)C)cc(OC)c1OC
Temperature: 35 °C
Reaction time: 36 h

Procedure:
5-(3,4,5-Trimethoxyphenyl)-2,4-dihydro-pyrazol-3-one (k, 2 g) in dry actonitrile (10 mL) was added C-tert-Butoxy-N,N,N′,N′-tetramethyl-methanediamine (3 mL) and stirred at 35° C. The reaction was monitored by HPLC. After 36 hours, the solid was filtered and rinsed with dry acetonitrile (5 mL) and dried under nitrogen pressure to yield the title compound (l).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH:29]=[CH:30][C:31]=1[CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[O:13][CH2:14][C:15]1[S:19][CH:18]=[C:17](/[C:20](/[CH2:27][CH3:28])=[CH:21]/[C:22](OCC)=[O:23])[CH:16]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH:29]=[CH:30][C:31]=1[CH2:32][O:33][Si:34]([C:37]([CH3:38])([CH3:40])[CH3:39])([CH3:35])[CH3:36])[O:13][CH2:14][C:15]1[S:19][CH:18]=[C:17](/[C:20](/[CH2:27][CH3:28])=[CH:21]/[CH2:22][OH:23])[CH:16]=1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2]
Reactant: CCOC(=O)/C=C(\CC)c1csc(COc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CC/C(=C\CO)c1csc(COc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)c1
Yield: 98.2 %

Procedure:
In a manner similar to that of Example 7(b), by reaction of 2.3 g (3.8 mmol) of ethyl (E)-3-{5-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]-3-thienyl}-2-pentenoate with 180 mg (4.7 mmol) of lithium aluminium hydride, the desired product (m=2.1 g; Y=100%) is obtained in the form of a colourless oil.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12](=O)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([Br:17])[CH:10]=3)[C:5](=O)[C:4]=2[CH:3]=1.[C:19]1([Li])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl.Cl[Sn]Cl>C1COCC1>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:2]3[CH:15]=[CH:14][CH:13]=[CH:4][CH:3]=3)[C:6]3[C:11]([C:12]=2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][C:9]([Br:17])=[CH:8][CH:7]=3)[CH:3]=1
Reactant: [Li]c1ccccc1
Reactant: O=C1c2ccc(Br)cc2C(=O)c2ccc(Br)cc21
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: C1CCOC1
Product: Brc1ccc2c(-c3ccccc3)c3cc(Br)ccc3c(-c3ccccc3)c2c1
Temperature: -75 °C
Reaction time: 2 h

Procedure:
36.6 g (100 mmol) of 2,6-dibromoanthraquinone are dissolved in 600 ml of THF, the solution is cooled to −75° C., and 100 ml of a 2 M phenyllithium solution in THF are added dropwise. After 2 h, the mixture is allowed to come to RT, 50 ml of 4 M HCl are added, the mixture is partitioned between toluene and water, the organic phase is dried over Na2SO4, and the solvent is removed in vacuo. The residue is taken up in 350 ml of DMF, 68 g (350 mmol) of SnCl2 are added, and the mixture is brought to an internal temperature of 140° C. for 2 h. 180 ml of 2 M HCl are then added at about 40° C., and the precipitate is filtered off with suction, washed with water, EtOH and ethyl acetate and dried at 80° C. in vacuo. Recrystallisation from toluene gives 30.8 g (63 mmol, 63%) of an ochre solid, which is homogeneous according to TLC and 1H-NMR and is employed in this form in the subsequent reaction.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[N+:12]([C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][CH:16]=1)([O-:14])=[O:13].Cl>N1C=CC=CC=1>[C:8]([C:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[O:11][C:19](=[O:20])[C:18]1[CH:17]=[CH:16][C:15]([N+:12]([O-:14])=[O:13])=[CH:23][CH:22]=1)(=[O:10])[CH3:9]
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: CC(=O)c1cc(Br)ccc1O
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)c1cc(Br)ccc1OC(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
5′-bromo-2′-hydroxyacetophenone (compound 1) (863 mg, 4.65 mmol) was added to a pyridine solution (20 ml) that contained 4-nitrobenzoyl chloride (1.00 g, 4.65 mmol) in an ice bath. The obtained mixture was reacted at room temperature for 30 minutes, and the reaction solution was then poured into 1 N hydrochloric acid under cooling on ice. The obtained mixture was intensively stirred. The obtained precipitate was collected by filtration, and the filtrate was then washed with purified water, so as to obtain a product of interest, 4-nitrobenzoic acid 2-acetyl-4-bromophenyl ester (compound 2). Yield: 1.57 g (yield constant: 92.7%) 1H NMR (300 MHz, CDCl3) δ 8.37 (s, 4H), 8.00 (s, 1H), 7.76-7.72 (m, 1H), 7.16 (d, J=8.7 Hz, 1H), 2.55 (s, 3H). MS m/z 365 (MH+).
Reaction SMILES: [CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:61])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53])[CH:47]([O:59][CH3:60])[CH2:46]2)[CH:8]([CH3:62])[CH:7]([OH:63])[CH2:6][C:5]1=[O:64])[CH:2]=[CH2:3].[C:65](OC(=O)C)(=[O:67])[CH3:66]>N1C=CC=CC=1>[C:65]([O:63][CH:7]1[CH2:6][C:5](=[O:64])[CH:4]([CH2:1][CH:2]=[CH2:3])[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:61])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:53])[CH3:54])[CH:47]([O:59][CH3:60])[CH2:46]2)[CH:8]1[CH3:62])(=[O:67])[CH3:66]
Reactant: CC(=O)OC(C)=O
Reactant: C=CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O[Si](C)(C)C(C)(C)C)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Solvent: c1ccncc1
Product: C=CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O[Si](C)(C)C(C)(C)C)C(OC)C3)C(C)C(OC(C)=O)CC1=O)C(C)CC2OC
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 17-allyl-12-[2-(4-tert-butyldimethylsilyloxy-3-methoxycyclohexyl)-1-methylvinyl]-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (39.9 mg) in pyridine (1.5 ml) was added acetic anhydride (0.5 ml), and the mixture was stirred at room temperature for 6 hours. The solvent was removed from the reaction mixture under reduced pressure to give a crude oil, which was purified on silica gel thin layer chromatography (developing solvent: diethyl ether and hexane, 1:1 v/v) to afford 14-acetoxy-17-allyl-12-[2-(4-tert-butyl-dimethylsilyloxy-3-methoxycyclohexyl)-1-methylvinyl]-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (26.5 mg).