Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)[CH2:6][NH:7][C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].Br[CH2:26][C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=1[C:37]1([O:45][CH3:46])[CH2:42][CH2:41][CH:40]([C:43]#[N:44])[CH2:39][CH2:38]1.Cl>C1COCC1.O>[F:18][C:17]([F:19])([F:20])[C:15]1[CH:14]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:16]=1)[CH2:6][N:7]([CH2:26][C:27]1[CH:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:30]=[CH:29][C:28]=1[C:37]1([O:45][CH3:46])[CH2:38][CH2:39][CH:40]([C:43]#[N:44])[CH2:41][CH2:42]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1
Reactant: Cn1nnc(NCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)n1
Reactant: COC1(c2ccc(C(F)(F)F)cc2CBr)CCC(C#N)CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC1(c2ccc(C(F)(F)F)cc2CN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2nnn(C)n2)CCC(C#N)CC1
Reaction time: 0.08 h
Yield: 119.4 %

Procedure:
To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazole-5-amine (285 mg, 0.877 mmol) in anhydrous THF (5 mL) was added sodium hydride (60% dispersion in mineral oil, 105 mg, 2.63 mol) and the mixture was stirred for 5 minutes then a solution of 4-(2 (bromomethyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile (330 mg, 0.877 mmol) in anhydrous THF (5 mL) was added. A further aliquot of sodium hydride (52 mg, 1.3 mmol) was added. The solution was stirred at room temperature for 72 hours. Water and 2 N HCl (5 mL) were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organics were dried with anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil (0.65 gm). This material was initially purified by flash chromatography on a 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-75% ethyl acetate in heptane) and finally purified on 1 mm silica gel rotor (Chromatotron, Harrison Research) (eluted with 20-70% dichloromethane in heptane) to yield the title compound as a colorless foam (134 mg, 24.6%). 1H NMR (400 MHz, CDCl3) δ 7.74 (s, H) 7.67(s, 2H) 7.44 (d, J=5.81 Hz, 2H) 7.29 (d, J=8.72 Hz, 1H) 5.01 (s, 2H) 4.76 (s, 2H) 4.15 (s, 3H) 2.87(s, 3H) 2.43(m, 1H) 2.20(d, J=12.45 Hz, 2H) 1.99(m, 2H) 1.55(m, 4H). LC-MS calc. 620, found 621.5 (M+H)
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26]O[CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(Cl)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.Cl.[F:51][C@@H]1CCNC1>>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26][C@@H:24]([F:51])[CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: F[C@@H]1CCNC1
Reactant: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Agent: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Agent: Cl
Product: CC(C)(C)c1nc(N2CC[C@@H](F)C2)c2nnn(Cc3ccccc3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-3-fluoropyrrolidine hydrochloride and isolated as light-yellow gum (9.8 mg, 54%). MS (m/e): 389.4 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:16])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1.[Cl:17][C:18]1[CH:31]=[CH:30][C:21]2[S:22][C:23]([S:26](Cl)(=[O:28])=[O:27])=[C:24]([CH3:25])[C:20]=2[CH:19]=1>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:16][S:26]([C:23]2[S:22][C:21]3[CH:30]=[CH:31][C:18]([Cl:17])=[CH:19][C:20]=3[C:24]=2[CH3:25])(=[O:28])=[O:27])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]1
Reactant: Cc1c(S(=O)(=O)Cl)sc2ccc(Cl)cc12
Reactant: COc1cc(N)ccc1N1CCN(C)CC1
Solvent: ClCCl
Product: COc1cc(NS(=O)(=O)c2sc3ccc(Cl)cc3c2C)ccc1N1CCN(C)CC1
Reaction time: 8 h
Yield: 33.6 %

Procedure:
A solution of 3-methoxy-4-(4-methylpiperazin-1-yl)phenylamine (D35) (50 mg, 0.23 mmol) and 5-chloro-3-methylbenzo[b]thiophene-2-sulfonyl chloride (64 mg, 0.23 mmol) in dichloromethane (2 ml) was allowed to stand at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed with potassium carbonate (aq), which was back-extracted with further dichloromethane. The combined organic phases were dried (Na2SO4) and evaporated under reduced pressure to give a crude product, which was purified by chromatography on silica gel, eluting with methanol and dichloromethane. This gave the title compound (E128) as an off-white solid (36 mg, 34%) MH+=466.
Reaction SMILES: [CH2:1]([C:5]12[CH2:17][CH:16]([I:18])[C:15](=[O:19])[C:14]([CH3:20])=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:21]COC)=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4].Cl.C([O-])(O)=O.[Na+]>CO.CCOC(C)=O>[CH2:1]([C:5]12[CH2:17][CH:16]([I:18])[C:15](=[O:19])[C:14]([CH3:20])=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC12Cc3cc(OCOC)ccc3C1=C(C)C(=O)C(I)C2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCCC12Cc3cc(O)ccc3C1=C(C)C(=O)C(I)C2
Temperature: 70 °C

Procedure:
A suspension of (2SR,9aRS)-9a-butyl-2-iodo-7-methoxymethoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (50 mg, 0.11 mmol) in methanol (3.5 mL) was placed under a nitrogen atmosphere, heated in an oil bath at 70° C. to affect solution, then treated with 2N aqueous HCl (0.195 mL, 0.39 mmol). The resulting solution was stirred and heated in an oil bath at 70° C. for 50 minutes. After cooling to room temperature, the mixture was diluted with EtOAc and shaken with 5% aqueous NaHCO3. The aqueous portion was separated and extracted with EtOAc. The combined organics were washed with water and brine, dried over MgSO4, filtered, and concentrated under vacuum to an oil. The crude product was purified by PLC on a 0.1×20×20 cm silica gel GF plate, developing twice with 5:1 hexanes-EtOAc. The band at Rf 0.24-0.32 was eluted with EtOAc and the eluant evaporated under vacuum to provide (2SR,9aRS)-9a-butyl-7-hydroxy-2-iodo-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one as an oil.
Reaction SMILES: Cl.[NH2:2][C:3](=[NH:18])[N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:5]1.[Cl:19][C:20]([SH:23])(Cl)Cl.[OH-].[Na+]>ClCCl.O>[Cl:19][C:20]1[S:23][N:2]=[C:3]([N:4]2[CH2:5][CH2:6][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:8][CH2:9]2)[N:18]=1
Reactant: CC(C)(C)OC(=O)NC1CCN(C(=N)N)CC1
Reactant: SC(Cl)(Cl)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1CCN(c2nsc(Cl)n2)CC1
Temperature: 25 °C
Yield: 34.4 %

Procedure:
To a solution of tert-butyl {1-[amino(imino)methyl]piperidin-4-yl}carbamate hydrochloride (1.50 g, 5.38 mmol) and perchloromethyl mercaptan (0.578 ml, 5.38 mmol) in dichloromethane (20 ml) was added dropwise a solution of sodium hydroxide (0.861 g, 21.5 mmol) in water (2.5 ml) under ice-cooling. Then, the reaction mixture was stirred under ice-cooling for 1 hour and at room temperature for 1 hour. The organic layer was separated, washed with water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give 590 mg (34.3%) of the desired product as a solid.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[CH:5][CH:4]=1)=O.[S:16]1[CH2:20][C:19](=[O:21])[NH:18][C:17]1=[O:22].N1CCCCC1.C(O)(=O)C1C=CC=CC=1>C1(C)C=CC=CC=1.O>[Cl:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH:1]=[C:20]2[S:16][C:17](=[O:22])[NH:18][C:19]2=[O:21])=[CH:4][CH:5]=1
Reactant: O=C1CSC(=O)N1
Reactant: O=Cc1ccc(-c2ccccc2Cl)cc1
Agent: O=C(O)c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Solvent: C1CCNCC1
Product: O=C1NC(=O)C(=Cc2ccc(-c3ccccc3Cl)cc2)S1

Procedure:
To a solution of 4-formyl-(2′-chloro-1,1′-biphenyl) (0.12 g, 0.55 mmol) and 2,4-thiazolidinedione (0.08 g, 0.65 mmol) in toluene (10 mL) were added piperidine (0.008 mL, 0.073 mMol) and benzoic acid (0.011 mg, 0.08 mmol), and the reaction was refluxed for 4 h with continuous removal of water. The solvent was then distilled off and the oily residue obtained was purified by chromatography on silica-gel using hexane: ethyl acetate (3:1) as the eluent to yield titled product.
Reaction SMILES: [O:1]=[C:2]([O-:13])[C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[Ca+2:14].[O:15]=[C:16]([O-:27])[C@@H:17]([C@H:19]([C@@H:21]([C@@H:23]([CH2:25][OH:26])[OH:24])[OH:22])[OH:20])[OH:18].[B:28](O)(O)[OH:29]>O>[B:28]1([OH:29])[O:8][CH:7]([CH:5]([OH:6])[CH:3]([OH:4])[C:2]([O-:13])=[O:1])[CH:9]([CH2:11][OH:12])[O:10]1.[B:28]1([OH:29])[O:22][CH:21]([CH:19]([OH:20])[CH:17]([OH:18])[C:16]([O-:27])=[O:15])[CH:23]([CH2:25][OH:26])[O:24]1.[Ca+2:14]
Reactant: OB(O)O
Reactant: O=C([O-])[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: [Ca+2]
Solvent: O
Product: O=C([O-])C(O)C(O)C1OB(O)OC1CO
Temperature: 50 °C

Procedure:
860.5 grams of calcium gluconate monohydydrate and 244 grams of technical grade boric acid were added to 1100 grams of water at room temperature. The resultant mixture was stirred and warmed to a temperature of about 50° C. until a dark brown solution was obtained. The solution was allowed to cool to room temperature. The solution can be used as is or the water can be evaporated to provide the calcium borogluconate as a brownish solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:40])[NH:7][C@@H:8]([CH2:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]([F:39])[CH:33]=1)[C@@H:9]([OH:30])[CH2:10][C@H:11]([C:14](N1[C@H]2C3C=CC=CC=3C[C@H]2OC1(C)C)=[O:15])[CH2:12][CH3:13])([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl>[C:1]([O:5][C:6](=[O:40])[NH:7][C@H:8]([C@@H:9]1[CH2:10][C@@H:11]([CH2:12][CH3:13])[C:14](=[O:15])[O:30]1)[CH2:31][C:32]1[CH:33]=[C:34]([F:39])[CH:35]=[C:36]([F:38])[CH:37]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC[C@H](C[C@H](O)[C@H](Cc1cc(F)cc(F)c1)NC(=O)OC(C)(C)C)C(=O)N1[C@H]2c3ccccc3C[C@H]2OC1(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: O
Product: CC[C@@H]1C[C@@H]([C@H](Cc2cc(F)cc(F)c2)NC(=O)OC(C)(C)C)OC1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
(1S,2S, 4R)-[1-(3,5-Difluorobenzyl)-4-((3aS, 8aR)-2,2-dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazole-3-carbonyl)-2-hydroxyhexyl]-carbamic acid tert-butyl ester (VIII, 60 mg) was dissolved in 5:1 toluene/CH2Cl2 (3 mL), and p-toluenesulfonic acid monohydrate (23 mg) was added. This was stirred at rt for 18 h. The mixture was then filtered, and partitioned between half-saturated NaHCO3 (3 mL) and 1:1 EtOAc/hexanes (2×3 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure. Flash chromatography of the residue afforded desired product as a solid: MH+370.2.
Reaction SMILES: [CH3:1][CH:2]([NH:4][CH2:5][CH:6]([OH:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH2:18])=[O:17])=[CH:11][CH:10]=1)[CH3:3]>C(#N)C.C(O)(=O)C>[CH3:3][CH:2]([NH:4][CH2:5][C@H:6]([OH:19])[CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([NH2:18])=[O:17])=[CH:13][CH:14]=1)[CH3:1]
Reactant: CC(C)NCC(O)COc1ccc(CC(N)=O)cc1
Solvent: CC(=O)O
Solvent: CC#N
Product: CC(C)NC[C@H](O)COc1ccc(CC(N)=O)cc1

Procedure:
20 μg (R,S)-atenolol is injected in 20 μl of the eluant acetonitrile/acetic acid (v/v, 93/7). k'R =1.18 k'S =2.34 α=2.0 RS =0.5
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:12]2[CH:13]=[CH:14][C:15]3[C:21](=[O:22])[NH:20][C:19]4[CH:23]=[C:24]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])[CH:25]=[CH:26][C:18]=4[NH:17][C:16]=3[CH:32]=2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].O[NH:34][C:35](=[NH:37])[CH3:36].CC(C)N=C=NC(C)C>CN(C=O)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:12]2[CH:13]=[CH:14][C:15]3[C:21](=[O:22])[NH:20][C:19]4[CH:23]=[C:24]([CH2:27][CH2:28][C:29]([O:31][NH:37][C:35](=[NH:34])[CH3:36])=[O:30])[CH:25]=[CH:26][C:18]=4[NH:17][C:16]=3[CH:32]=2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]
Reactant: COc1cc(-c2ccc3c(c2)Nc2ccc(CCC(=O)O)cc2NC3=O)ccc1[N+](=O)[O-]
Reactant: CC(=N)NO
Agent: CC(C)N=C=NC(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cc(-c2ccc3c(c2)Nc2ccc(CCC(=O)ONC(C)=N)cc2NC3=O)ccc1[N+](=O)[O-]
Reaction time: 8 h

Procedure:
A mixture of Example 230 (65 mg, 0.15 mmol), N-hydroxy-acetamidine (14 mg, 0.18 mmol) in 1 mL of DMF was treated with DIC in 1 mL of CH2Cl2 at 0° C. The reaction mixture was stirred overnight and partitioned between EtOAc and water. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 100:1 ethyl acetate/MeOH to provide the desired product. MS (DCI) m/e 490 (M+H)+; 1H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H), 8.01 (d, J=8.29 Hz, 1H), 7.94 (s, 1H), 7.79 (d, J=8.29 Hz, 1H), 7.52 (d, J=1.23 Hz, 1H), 7.33-7.34 (m, 2H), 7.29 (m, 1H), 6.93 (m, 1H), 6.83-6.85 (m, 2H), 6.27 (s, 2H), 4.03 (s, 3H), 2.73-2.76 (m, 2H), 2.58-2.62 (m, 2H), 1.72 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:12].N1C=CN=C1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C(Cl)Cl.CCOC(C)=O>[C:21]([Si:18]([O:12][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:10])([F:11])[F:9])[C:2]=1[Cl:1])([CH3:20])[CH3:19])([CH3:24])([CH3:23])[CH3:22]
Reactant: Oc1cccc(C(F)(F)F)c1Cl
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1cccc(C(F)(F)F)c1Cl
Reaction time: 0.08 h
Yield: 99.4 %

Procedure:
To a solution of 2-chloro-3-trifluoromethyl-phenol (509 mg, 2.59 mmol) in CH2Cl2 (20 mL) was added imidazole (264 mg, 3.88 mmol). The mixture was stirred for 5 minutes, to which was added portionwise tert-butyldimethylsilyl chloride (467 g, 3.1 mmol). The mixture was stirred for 2 hours at room temperature and was diluted with EtOAc. The crude mixture was washed with 1N HCl, water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give tert-butyl-(2-chloro-3-trifluoromethyl-phenoxy)-dimethyl-silane (800 mg, 99%).
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:10]=[C:11]([CH:17]=[C:18]([S:27](=[O:30])(=[O:29])[NH2:28])[C:19]=1[S:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:12]([O:14]CC)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C(O)C>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]([CH:17]=[C:18]([S:27](=[O:30])(=[O:29])[NH2:28])[C:19]=1[S:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1cc(SCc2ccccc2)c(Sc2ccccc2)c(S(N)(=O)=O)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: NS(=O)(=O)c1cc(C(=O)O)cc(SCc2ccccc2)c1Sc1ccccc1
Reaction time: 0.17 h

Procedure:
A mixture of ethyl 3-benzylthio-4-phenylthio-5-sulfamylbenzoate (0.35 g), 1 N sodium hydroxide (10 ml), and ethanol (5 ml) is stirred for 10 minutes. The resulting solution is boiled for 2 minutes and is thereafter left for 1 hour to reach room temperature. 1 N hydrochloric acid (10.5 ml) is added to precipitate 3-benzylthio-4-pnenylthio-5-sulfamylbenzoic acid. After collection by filtration and recrystallization from aqueous ethanol the compound is obtained with a melting point of 208° - 209°C.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([C:9]2(O)[CH:16]3[CH2:17][CH:12]4[CH2:13][CH:14]([CH2:18][CH:10]2[CH2:11]4)[CH2:15]3)[CH:6]=[CH:7][CH:8]=1)[CH3:2].C[Si]([C:24]#[N:25])(C)C.B(F)(F)F.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[CH2:1]([C:3]1[CH:4]=[C:5]([C:9]2([C:24]#[N:25])[CH:16]3[CH2:17][CH:12]4[CH2:13][CH:14]([CH2:18][CH:10]2[CH2:11]4)[CH2:15]3)[CH:6]=[CH:7][CH:8]=1)[CH3:2]
Reactant: CCc1cccc(C2(O)C3CC4CC(C3)CC2C4)c1
Reactant: C[Si](C)(C)C#N
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCc1cccc(C2(C#N)C3CC4CC(C3)CC2C4)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 81.3 %

Procedure:
A solution of 2-(3-ethylphenyl)-2-adamantanol (1.82 g, 7.14 mmol) in dry CHCl3 (5 mL) under argon, was treated with trimethylsilyl cyanide (1.00 mL, 7.5 mmol), cooled to 0° C., treated with BF3 etherate (1.10 mL, 8.57 mmol), allowed to warm to room temperature and stirred for 2 h. The mixture was treated with dilute NaHCO3 (10 mL), extracted with CHCl3 (2×10 mL), the combined extracts washed with water (10 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography [SiO2; heptane-EtOAc (9:1)] to give the product (1.54 g, 82%) as a colourless oil: IR νmax (thin film)/cm−1 2922, 2860, 2226, 1604, 1487, 1453, 1105, 799 and 704; NMR δH (400 MHz, CDCl3) 1.24 (3H, t, J 7.5 Hz), 1.62-1.65 (2H, m), 1.70-1.82 (5H, m), 1.98-204 (3H, m), 2.45-2.48 (2H, m), 2.66 (2H, q, J 7.5 Hz), 2.79 (2H, s), 7.15 (1H, d, J 7.5 Hz) and 7.25-7.34 (3H, m); Anal. Calcd for C19H23N: C, 85.99; H, 8.73; N, 5.28. Found: C, 85.85; H, 8.77; N, 5.23.
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH2:10][S:9][C:8]2=[S:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([O:18][CH2:19][CH2:20]CC)[CH2:15][CH2:16][CH3:17]>>[CH2:19]([O:18][C:14](=[C:10]1[S:9][C:8](=[S:13])[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]1=[O:12])[CH2:15][C:16]1[CH:17]=[CH:3][CH:2]=[CH:1][CH:6]=1)[CH3:20]
Reactant: CCCCOCCCC
Reactant: O=C1CSC(=S)N1c1ccccc1
Product: CCOC(Cc1ccccc1)=C1SC(=S)N(c2ccccc2)C1=O
Reaction time: 0.5 h

Procedure:
Alternatively, a mixture of 6 g. (0.029 m.) of 3-phenyl-rhodanine, 15 g. (0.063 m.) of triethylorthophenylacetate and 15 ml. of n-butyl ether is heated to reflux and then distillate is removed until the temperature of the mixture reaches 150°C. After heating at this temperature for one hour, an additional 5 g. of orthoester is added and heating is continued for 30 minutes. To the reaction mixture is added 5 ml. of acetic anhydride and heating is continued for 5 minutes. The resulting mixture is concentrated in vacuo and the residue is eluted through a column of silica gel with 2:1-cyclohexane-benzene. The product from the first eluates give 5-(1'-ethoxy-2'-phenylethylidene)-3-phenylrhodanine, m.p. 119°-121°C. Alkaline hydrolysis as described above of this intermediate furnishes the identical hydroxy derivative.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:37])[C:4]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:8]([CH3:20])[C:7]=1[CH2:21][O:22][C:23](=[O:25])[CH3:24].C(OC(=O)[C@H](C(COC(=O)C)C1C=CC(NC(OC(C)(C)C)=O)=C(C)C=1)CC(OCC)=O)C>CO.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:37])[C@H:4]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])=[C:8]([CH3:20])[C:7]=1[CH2:21][O:22][C:23](=[O:25])[CH3:24]
Reactant: COC(=O)C(=Cc1ccc(NC(=O)OC(C)(C)C)c(C)c1COC(C)=O)NC(=O)OCc1ccccc1
Agent: CCOC(=O)C[C@H](C(=O)OCC)C(COC(C)=O)c1ccc(NC(=O)OC(C)(C)C)c(C)c1
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)[C@@H](Cc1ccc(NC(=O)OC(C)(C)C)c(C)c1COC(C)=O)NC(=O)OCc1ccccc1
Yield: 97 %

Procedure:
A solution of 3-(2-acetoxymethyl-4-tert-butoxycarbonylamino-3-methyl-phenyl)-2-benzyloxycarbonylamino-acrylic acid methyl ester (2.51 g, 4.9 mmol) in methanol (50 mL) and ethyl acetate (15 mL) was reacted in a manner similar to the preparation of 2-(S)-(acetoxymethyl-4-tert-butoxycarbonylamino-3-methyl-benzyl)-succinic acid diethyl ester. Title compound was obtained as an off-white solid in 97% yield. 1H NMR (300 MHz, CDCl3): δ=7.66 (d, J=7.9, 1H), 7.31 (m, 5H), 6.99 (d, J=8.5, 1H), 6.21 (s, 1H), 5.31 (d, J=7.6, 1H), 5.17 (d, J=3.7, 2H), 5.04 (d, J=5.80, 2H), 4.56 (m, 1H), 3.71 (s, 3H), 3.23 (dd, J1=5.80, J2=14.7, 1H), 3.07 (dd, J1=7.8, J2=14.2, 1H), 2.21 (s, 3H), 2.00 (s, 3H), 1.50 (s, 9H). MS m/e (M−H)−=513.0.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18].[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]1[CH2:26][CH2:27][N:28]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]23[CH2:17][CH2:16][CH2:15][C:13]4[C:14]2=[C:9]([CH:10]=[CH:11][CH:12]=4)[NH:8][C:7]3=[O:18])[CH2:29][CH2:30]1
Reactant: O=C1Nc2cccc3c2C1(CCCCBr)CCC3
Reactant: c1ccc(N2CCNCC2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1Nc2cccc3c2C1(CCCCN1CCN(c2ccccn2)CC1)CCC3
Yield: 100 %

Procedure:
2a-(4-Bromobutyl)-2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (147 mg, 0.48 mmol), 1-(2-pyridyl)piperazine (86 mg, 0.53 mmol) and potassium carbonate (99 mg, 0.72 mmol) were stirred overnight in anhydrous N,N-dimethylformamide (2 ml) at 60° C. The solvent was evaporated under a reduced pressure, and the thus obtained residue was mixed with ethyl acetate and water. The reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate, the solvent was evaporated under a reduced pressure and then the thus obtained substance was separated and purified by a silica gel column chromatography to obtain 190 mg of the title compound (0.48 mmol, 100% in yield).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14]([OH:16])=O)[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.[CH3:21][NH:22][CH3:23].O1CCCC1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[O:16])[N:22]([CH3:23])[CH3:21])[N:13]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)Nc1nc(C(=O)O)cs1
Reactant: CNC
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Solvent: O=S(Cl)Cl
Product: CN(C)C(=O)c1csc(NC(=O)OC(C)(C)C)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 75 %

Procedure:
To a suspension of 2-tert-butoxycarbonylamino-thiazole-4-carboxylic acid (prepared as described in example 15) (183 mg, 0.75 mmol) in toluene (7 mL) was added thionyl chloride (2.2 mL, 30 mmol) and the mixture heated to reflux under argon for 2.5 hours. The mixture was then concentrated in vacuo, the residue suspended in dichloromethane (7 mL), a 2 M solution of dimethylamine in tetrahydrofuran (0.5 mL, 1 mmol) added and the mixture stirred at ambient temperature under argon overnight. The reaction mixture was concentrated in vacuo, the residue suspended in ethyl acetate and the solid removed by filtration. The filtrate was concentrated in vacuo and the residue purified by chromatography over silica gel eluted with 1% v/v methanol in ethyl acetate to give (4-dimethylcarbamoyl-thiazol-2-yl)-carbamic acid tert-butyl ester as a colorless solid (152 mg, 75%).