Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:45][CH:46]1[C:72](=[O:73])[N:48]2[C:49]([C:69]([OH:71])=[O:70])=[C:50]([CH2:53][S:54][C:55]3[S:56][C:57]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:58][N:59]=3)[CH2:51][S:52][C@H:47]12>C(OCC)(=O)C.O.CN(C)C=O>[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[Cl-:3].[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([NH:45][CH:46]2[C:72](=[O:73])[N:48]3[C:49]([C:69]([OH:71])=[O:70])=[C:50]([CH2:53][S:54][C:55]4[S:56][C:57]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[N:58][N:59]=4)[CH2:51][S:52][C@H:47]23)=[O:17])[N:13]=1)=[O:7]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)NCc1nnc(SCC2=C(C(=O)O)N3C(=O)C(N)[C@H]3SC2)s1
Reactant: CC(C)(C)OC(=O)NCCCON=C(C(=O)O)c1csc(NC=O)n1
Agent: C[N+](C)=CCl
Agent: C[Si](C)(C)CC(N)=O
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCCON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSc3nnc(CNC(=O)OC(C)(C)C)s3)CS[C@H]12)c1csc(NC=O)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Vilsmeier reagent was prepared from N,N-dimethyl-formamide (0.65 g.) and phosphoryl chloride (1.4 g.) in a usual manner. 2-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetic acid (syn isomer, 3.0 g.) was added to a stirred suspension of the Vilsmeier reagent in ethyl acetate (30 ml.) under ice-cooling and stirred at the same temperature for 30 minutes [Solution A]. Trimethylsilylacetamide (8.1 g.) was added to a stirred suspension of 7-amino-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (3.7 g.) in ethyl acetate (40 ml.) and stirred at room temperature for 30 minutes. The solution A was added to the solution all at once at -30° C., and stirred at -10° to -40° C. for an hour. Water and ethyl acetate (100 ml.) were added to the resultant mixture at -10° C., and the ethyl acetate layer was separated. Water (100 ml.) was added to the ethyl acetate layer and adjusted to pH 7.0 with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated. Ethyl acetate was added to the solution and adjusted to pH 3.8 with 10% hydrochloric acid under ice-cooling. The ethyl acetate layer was separated and washed with saturated sodium chloride solution. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diisopropyl ether to give 7-[2-(2-formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.6 g.).
Reaction SMILES: Cl.Cl.Cl.[NH2:4][C@@H:5]([C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[CH2:14][CH2:13]1)=[O:11])[CH2:6][C:7](=[O:9])[NH2:8].[Cl:25][C:26]1[CH:27]=[CH:28][C:29]2[CH:33]=[C:32]([C:34](O)=[O:35])[S:31][C:30]=2[CH:37]=1>>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]2[CH:33]=[C:32]([C:34]([NH:4][C@@H:5]([C:10]([N:12]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]4)[CH2:14][CH2:13]3)=[O:11])[CH2:6][C:7](=[O:9])[NH2:8])=[O:35])[S:31][C:30]=2[CH:37]=1
Reactant: CN1CCC(N2CCN(C(=O)[C@H](N)CC(N)=O)CC2)CC1
Reactant: O=C(O)c1cc2ccc(Cl)cc2s1
Agent: Cl
Product: CN1CCC(N2CCN(C(=O)[C@@H](CC(N)=O)NC(=O)c3cc4ccc(Cl)cc4s3)CC2)CC1

Procedure:
Using methods substantially equivalent to those described in Method D-1, the subtitled compound was prepared from 1-(D-asparaginyl)-4-(1-methylpiperidin-4-yl)piperazine trihydrochloride and 6-chlorobenzo[b]thiophene-2-carboxylic acid (40%).
Reaction SMILES: [C:1]1([CH3:16])[CH:6]=[CH:5][C:4]([NH:7][C:8]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[O:17]([C:19]#N)[Na].Cl.[OH2:22]>C(O)(=O)C>[C:1]1([CH3:16])[CH:6]=[CH:5][C:4]([N:7]2[C:8]3([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]3)[C:14](=[O:22])[NH:15][C:19]2=[O:17])=[CH:3][CH:2]=1
Reactant: O
Reactant: N#CO[Na]
Reactant: Cc1ccc(NC2(C#N)CCCCC2)cc1
Agent: Cl
Solvent: CC(=O)O
Product: Cc1ccc(N2C(=O)NC(=O)C23CCCCC3)cc1
Temperature: 35 °C
Reaction time: 2 h

Procedure:
18 g of 1-p-tolylaminocyclohexanecarbonitrile are dissolved in 90 ml of acetic acid in a 250 ml three-necked flask, at room temperature and under nitrogen, the mixture is heated to 35° C., 8.74 g of NaOCN are then added portionwise, heating is continued up to 60° C. and the mixture is stirred for 2 hours. 29 ml of 12N HCl and then 19 ml of water are introduced into the reaction medium, which is then heated for 30 minutes from 50 to 90° C. The reaction medium is transferred into about 1 l of water and a white precipitate forms, which is recovered by filtration and then dried. The product 1-p-tolyl-1,3-diazaspiro[4.5]decane-2,4-dione is obtained in the form of a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21]([C:23]3[C:24](F)=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:30][CH2:31][C:32]1[CH:37]=[CH:36][N:35]=[C:34]2[N:38](C(=O)C)[CH:39]=[CH:40][C:33]=12.CCN(C(C)C)C(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21]([C:23]3[C:24]([NH:30][CH2:31][C:32]4[CH:37]=[CH:36][N:35]=[C:34]5[NH:38][CH:39]=[CH:40][C:33]=45)=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1Cc2cc(NC(=O)c3cccnc3F)ccc2C(C)(C)C1
Reactant: CC(=O)n1ccc2c(CN)ccnc21
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1Cc2cc(NC(=O)c3cccnc3NCc3ccnc4[nH]ccc34)ccc2C(C)(C)C1

Procedure:
A mixture of 7-[(2-fluoro-pyridine-3-carbonyl)-amino]-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.24 g), 1-(4-aminomethyl-pyrrolo[2,3-b]pyridin-1-yl)-ethanone (0.14 g), DIEA (0.8 mL) and IpOH (0.8 mL) was subjected to a MicroWave condition (170° C., 1000 s) twice. Evaporation of solvent yielded the crude compound, which was purified by chromatography through silica gel (15 g, 5% MeOH/CH2Cl2) to afford 4,4-dimethyl-7-({2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-pyridine-3-carbonyl}-amino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[NH:11][CH:10]([C:12]([OH:14])=O)[CH2:9][S:8]2)[CH:2]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[NH:11][CH:10]([C:12]([N:24]3[CH2:25][CH2:26][N:21]([C:16]4[N:15]=[CH:20][CH:19]=[CH:18][N:17]=4)[CH2:22][CH2:23]3)=[O:14])[CH2:9][S:8]2)[CH:2]=1
Reactant: O=C(O)C1CSC(c2cccnc2)N1
Reactant: c1cnc(N2CCNCC2)nc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(C1CSC(c2cccnc2)N1)N1CCN(c2ncccn2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-(3-pyridyl)thiazolidine-4-carboxylic acid 2.1 g, 1-(2-pyrimidinyl)piperazine.2 hydrochyloride 2.2 g, triethylamine 1.8 g, 1-hydroxybenzotriazole 1.5 g and N,N-dimethylformamide 30 ml was added dicyclohexylcarbodiimide 2.0 g under cooling and the mixture was stirred overnight at room temperature. The resultant dicyclohexylurea was distilled off, ethyl acetate 100 ml and water 50 ml were added to the filtrate and the solution was basified by addition of potassium carbonate. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The organic layer and extract were combined, washed successively with water and saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethanol to give 0.8 g of 1-[2-(3-pyridyl)thiazolidine-4-ylcarbonyl]-4-(2-pyrimidinyl)piperazine.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][CH3:14])[CH:6]=[CH:5]2.[Cl:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1>>[CH2:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:15])[CH:21]=3)=[CH:10][CH:9]=2)[CH:5]=[CH:6]1)[CH2:12][CH2:13][CH3:14]
Reactant: CCCCn1ccc2cc(Br)ccc21
Reactant: OB(O)c1cccc(Cl)c1
Product: CCCCn1ccc2cc(-c3cccc(Cl)c3)ccc21

Procedure:
The title compound was prepared from 5-bromo-1-butyl-1H-indole (Step 1 of Example 29) and 3-chlorophenylboronic acid in substantially the same manner, as described in Step 2 of Example 25. The product was obtained as an oil. Mass spectrum (APCI, [M+H]+) m/z 284. 1HNMR (400 MHz, DMSO-d6): δ 7.85 (s, 1H), 7.69 (s, 1H), 7.63 (d, 1H, J=8.36 Hz), 7.55 (d, 1H, J=8.55 Hz), 7.47-7.41 (m, 3H), 7.34 (d, 1H, J=7.94 Hz), 6.48 (d, 1H, J=3.05 Hz), 4.19 (t, 2H, J=7.01 Hz), 1.73 (p, 2H, J=7.16 Hz), 1.25 (h, 2H, J=7.46 Hz), and 0.88 ppm (t, 3H, J=7.31 Hz). Elemental Analysis for C18H18ClN: Calculated: C, 76.18; H, 6.39; N, 4.94. Found: C, 76.85; H, 6.23; N, 4.81.
Reaction SMILES: [C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[O:10][C:9]([C:18]2[N:19]=[CH:20][C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2].[F-].[Cs+].[CH:30](/B(O)O)=[CH:31]\[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>COCCOC.CO.ClCCl.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>[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13](/[CH:30]=[CH:31]/[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:14][CH:15]=2)[O:10][C:9]([C:18]2[N:19]=[CH:20][C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)/C=C/c1ccccc1
Reactant: CC(C)(C)ON=c1cc(-c2cc3ccccc3cn2)oc2cc(Br)ccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Solvent: ClCCl
Solvent: CO
Product: CC(C)(C)ON=c1cc(-c2cc3ccccc3cn2)oc2cc(/C=C/c3ccccc3)ccc12
Temperature: 150 °C
Yield: 76.2 %

Procedure:
In a microwave vial, a solution of 7-bromo-2-isoquinolin-3-yl-chromen-4-one O-tert-butyl oxime (200 mg, 0.47 mmol), cesium fluoride (213 mg, 1.41 mmol) and trans-styryl boronic acid (160 mg, 1.07 mmol) in 1,2-dimethoxyethane (3.2 ml) and methanol (1.6 ml) was degassed with argon for 20 min and then tetrakis(triphenylphosphine)palladium (30 mg, 0.026 mmol) was added. The vial was sealed and the mixture was heated under microwave irradiation to 150° C. for 5 min. After cooling, the solution was diluted with dichloromethane and absorbed over silica gel for purification by flash chromatography (gradient cyclohexane/dichloromethane: 0-80%) to yield 2-Isoquinolin-3-yl-7-((E)-styryl)-chromen-4-one O-tert-butyl oxime (160 mg, 76%) as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH2:11])=[S:10])=[CH:4][CH:3]=1.S(Cl)(Cl)(=O)=O>ClC1C=CC=CC=1>[NH2:11][C:9]1[S:10][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=2[N:8]=1
Reactant: NC(=S)Nc1ccc(Cl)cc1
Solvent: O=S(=O)(Cl)Cl
Solvent: Clc1ccccc1
Product: Nc1nc2ccc(Cl)cc2s1
Reaction time: 3 h
Yield: 85 %

Procedure:
186.5 parts of 4-chlorophenylthiourea were suspended with stirring in 850 parts of chlorobenzene, and 185 parts of sulfuryl chloride were added uniformly with stirring at a temperature of 40°-45° C. within about 3 hours. After the immediately starting gas development had ceased, the suspension formed which could be stirred with difficulty only was liberated from the chlorobenzene by steam distillation. The remaining suspension of 2-amino-6-chlorobenzothiazolium chloride was adjusted to pH 8 with 25% ammonia solution, thus causing the crude 2-amino-6-chlorobenzothiazole to agglomerate to a tacky mass. By decantation and drying, 146.3 parts of 2-amino-6-chlorobenzothiazole containing about 85% of pure product were obtained (=124.4 parts of 100% product, 67.4% of th.).
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[NH:10][C:11]([N:13]1[CH:17]=[CH:16]N=C1)=[S:12].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](CCN)=[CH:21][CH:20]=1.C(OCC)(=O)C>CN(C)C=O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:16][CH2:17][NH:13][C:11]([NH:10][C:2]2[NH:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)=[S:12])=[CH:21][CH:20]=1
Reactant: NCCc1ccc(Cl)cc1
Reactant: S=C(Nc1nc2ccccc2[nH]1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: S=C(NCCc1ccc(Cl)cc1)Nc1nc2ccccc2[nH]1
Temperature: 25 °C
Yield: 79.2 %

Procedure:
A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(4-chlorophenyl)ethylamine (0.79 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90° C. for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, 1N aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 1.31 g (79%) of the titled product as a white solid: mp 173°-182° C.; IR (KBr, cm-1) 3168, 3031, 1668, 1562, 1494, 1470, 1327, 1221, 1174, 1090, 817, 777, 742, 657, 526, 457; 1H NMR (300 MHz, DMSO-d6) δ 12.18 (br s, 1H), 10.36 (br s, 1H), 7.52 (m, 2H), 7.22-7.38 (m, 7H), 3.76 (m, 2H), 2.89 (t, J=7 Hz, 2H); MS (FD) m/e 330 (M+), 332 (M+2); UV (EtOH) 301 nm (ε=21672), 293 nm (ε=22296), 266 nm (ε=13408), 260 nm (ε=12591), 206 nm (ε=29310).
Reaction SMILES: [Br:1][CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([I:17])=[CH:13][CH:12]=1)[C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[NH2:18][C:19]([NH2:21])=[S:20]>C(O)C>[BrH:1].[NH2:21][C:19]1[S:20][C:2]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([I:17])=[CH:13][CH:12]=2)=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[N:18]=1
Reactant: CCOC(=O)C(=O)C(Br)Cc1ccc(I)cc1
Reactant: NC(N)=S
Solvent: CCO
Product: Br
Product: CCOC(=O)c1nc(N)sc1Cc1ccc(I)cc1

Procedure:
Ethyl 3-bromo-4-(4-iodophenyl)-2-oxobutanoate (1.32 g) was dissolved in ethanol (26 ml), and then, thiourea (244 mg) was added to the solution. The reaction mixture was refluxed for 1 h under nitrogen atmosphere. The cooled reaction mixture was evaporated in vacuo. The crude material was triturated with diethyl ether to give ethyl 2-amino-5-(4-iodobenzyl)-1,3-thiazole-4-carboxylate hydrobromide as a pale yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]([CH3:16])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[N+:17]([O-])([OH:19])=[O:18].S(=O)(=O)(O)O>ClCCl>[CH3:16][C:9]1[C:8]([N+:17]([O-:19])=[O:18])=[C:3]([C:4]([O:6][CH3:7])=[O:5])[C:2]([CH3:1])=[CH:11][C:10]=1[C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)c1cc(C)c(C(=O)OC)cc1C
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: COC(=O)c1cc(C)c(C(=O)OC)c([N+](=O)[O-])c1C
Reaction time: 1.75 h
Yield: 74 %

Procedure:
Dimethyl 2,5-dimethylterephthalate (3.14 g, 14.1 mmol) was dissolved in dichloromethane (30 mL) and was cooled in an ice bath. Fuming nitric acid (7.6 mL) and concentrated sulfuric acid (0.92 mL) were added carefully, and the mixture was stirred for 1.75 h. The mixture was then quenched with water and diluted with dichloromethane. The aqueous portion was extracted with dichloromethane. The combined organic portion was dried over sodium sulfate, then filtered and concentrated to afford a yellow oil which was purified by column chromatography (silica gel, 10-20% ethyl acetate in hexanes) to afford dimethyl 2,5-dimethyl-3-nitroterephthalate (2.78 g, 10.4 mmol, 74% yield). 1H NMR (400 MHz, CDCl3): δ 7.85 (s, 1H), 3.94 (s, 3H), 3.89 (s, 3H), 2.49 (s, 3H), 2.46 (s, 3H); GCMS for C12H13NO6: 267 (M+).
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[C:14]2[CH2:18][C@H:19]([N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31])[CH3:20])C1C=CC=CC=1.O.C([O-])=O.[NH4+]>C(O)C.[Pd]>[OH:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[C:14]2[CH2:18][C@H:19]([N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31])[CH3:20]
Reactant: C[C@H](Cc1c[nH]c2c(OCc3ccccc3)cccc12)N1C(=O)c2ccccc2C1=O
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: C[C@H](Cc1c[nH]c2c(O)cccc12)N1C(=O)c2ccccc2C1=O
Temperature: 95 °C
Reaction time: 1 h

Procedure:
(R)-7-Benzyloxy-3-(2-phthalimidopropyl)indole 12.16 g was dissolved in 400 ml of ethanol, and a water 100 ml suspension of a 10% palladium on carbon catalyst (content 50%) 4.00 g prepared separately was added thereto. Ammonium formate 6.00 g was added thereto while stirring, and the suspension was heated in an oil bath of 95° C. For one hour. After cooling down, the catalyst was filtered off, and the filtrate was concentrated under reduced pressure. Acetone was added to the residue, and a deposited salt was filtered off. The filtrate was concentrated under reduced pressure, whereby 10.27 g of a residue containing the title compound was obtained.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:11][C:12]1([O:15][CH2:14]1)[CH3:13]>O1CCCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:11][C:12]([CH3:14])([OH:15])[CH3:13])=[CH:4][CH:3]=1
Reactant: CC1(C)CO1
Reactant: Sc1ccc(Br)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(O)CSc1ccc(Br)cc1
Reaction time: 1 h
Yield: 88.8 %

Procedure:
To a solution of 4-bromothiophenol (9.45 g, 50.0 mmol) in tetrahydrofuran (150 mL) was added sodium hydride (60% in oil, 2.20 g, 55.0 mmol) at 0° C. by small portions, and the resulting mixture was stirred for 1 hr. To this reaction mixture was added isobutylene oxide (4.91 mL, 55.0 mmol), and the resulting mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=1/1) to give the title compound (11.6 g, yield 89%) as a colorless oil.
Reaction SMILES: [CH:1]1(/[CH:4]=[N:5]/[S:6]([C:8]([CH3:11])([CH3:10])[CH3:9])=[O:7])[CH2:3][CH2:2]1.[F:12][CH:13]([F:23])[S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Na+].[Cl-]>C1COCC1>[CH:1]1([CH:4]([NH:5][S:6]([C:8]([CH3:11])([CH3:10])[CH3:9])=[O:7])[C:13]([F:12])([F:23])[S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:15])=[O:16])[CH2:2][CH2:3]1
Reactant: O=S(=O)(c1ccccc1)C(F)F
Reactant: CC(C)(C)S(=O)/N=C/C1CC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)S(=O)NC(C1CC1)C(F)(F)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of N-[(1E)-cyclopropylmethylene]-2-methylpropane-2-sulfinamide (1.0 g, 5.8 mmol) and [(difluoromethyl)sulfonyl]benzene (1.1 g, 5.8 mmol) in THF (60 mL) was added dropwise NaHMDS (2 M, 4 mL, 8.2 mmol) at −78° C. The reaction mixture was stirred at this temperature for 2 h. A saturated NaCl solution (60 mL) was added to the reaction mixture to quench the reaction at −78° C. After warmed to room temperature, the mixture was extracted with EtOAc. The combined organic phases were dried, concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (400 MHz, CDCl3) δ 7.80 (d, 2H); 7.60 (t, 1H); 7.48 (d, 2H); 3.48 (d, 1H); 1.06-1.10 (m, 1H); 1.05 (s, 9H); 0.45-0.75 (m, 4H).
Reaction SMILES: [C:1]([NH:8][CH:9]1[CH2:11][CH2:10]1)(OC(C)(C)C)=O.[CH2:12]([O:19][CH2:20][CH2:21]CBr)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[H-].[Na+].[Cl-:26].[NH4+]>CN(C=O)C>[ClH:26].[CH2:12]([O:19][CH2:20][CH2:21][CH2:1][NH:8][CH:9]1[CH2:10][CH2:11]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCCCOCc1ccccc1
Reactant: [Cl-]
Reactant: CC(C)(C)OC(=O)NC1CC1
Agent: [H-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cl
Product: c1ccc(COCCCNC2CC2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5° with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. After concentration, the residue is crystallized in ether. The crystals are filtered and washed with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H).
Reaction SMILES: [N+](C1C=CC(C[O:9][C:10]([C@@H:12]2[N:16]3[C:17](=[O:30])[C@@H:18]([NH:19][C:20](=[O:29])[C@H:21]([NH2:28])[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C@H:15]3[S:14][C@:13]2([CH2:32][O:33][C:34](=[O:39])[NH:35][C:36](=[O:38])[CH3:37])[CH3:31])=[O:11])=CC=1)([O-])=O.[H][H]>[Pd].O>[C:36]([NH:35][C:34]([O:33][CH2:32][C@@:13]1([CH3:31])[C@H:12]([C:10]([OH:11])=[O:9])[N:16]2[C:17](=[O:30])[C@@H:18]([NH:19][C:20](=[O:29])[C@H:21]([NH2:28])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:15]2[S:14]1)=[O:39])(=[O:38])[CH3:37]
Reactant: CC(=O)NC(=O)OC[C@]1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)OCc1ccc([N+](=O)[O-])cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Product: CC(=O)NC(=O)OC[C@]1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)O
Yield: 62.8 %

Procedure:
To a prehydrogenated suspension of 10% palladium on carbon (0.59 gm), water-washed ethyl acetate (6.0 ml) and water (3.0 ml) was added (2R,3S,5R,6R) 2-(N-acetyl)carbamoyloxymethyl-6-[(R)-2-amino-2-phenylacetamido]-2-methylpenam-3-carboxylic acid p-nitrobenzyl ester (0.59 gm. 1.06 mmol). The mixture was shaken at 50 psi hydrogen pressure for 3 hours at 25° and then filtered through Dicalite-coated paper. The aqueous phase was separated, concentrated at reduced pressure to remove volatile solvent and gases, frozen and lyophilized. There was obtained 0.30 gm of the title compound as an amorphous solid. The purity was estimated from its nmr spectrum to be 60-70%.