Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][O:15][CH3:16])[NH:11][CH2:10][C@H:9]1[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(#N)C.Br[CH2:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30]>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][O:15][CH3:16])[N:11]([CH2:28][C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH2:10][C@H:9]1[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C(CBr)OCc1ccccc1
Reactant: COC[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C)CN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: COC[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C)CN1CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 91.3 %

Procedure:
To a stirred suspension of (2R,5R)-5-methoxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (11 g, 45 mmol), potassium carbonate (6.79 g, 49.14 mmol) and acetonitrile (48 mL) was added benzyl bromoacetate (7.08 mL, 44.67 mmol) dropwise at ambient temperature. The reaction was stirred for 18 h at ambient temperature, then diluted with chloroform (150 mL), filtered and the filtrate concentrated. The crude oil was purified by column chromatography on silica gel (gradient elution, 0-70%, EtOAc/petrol), to give the title compound (16 g, 92%) as a pale yellow oil. 1H NMR (Me-d3-OD): 7.45-7.22 (5H, m), 5.21-5.12 (2H, m), 4.84 (2H, s), 4.16-4.03 (1H, m), 3.91 (1H, d), 3.62 (1H, d), 3.56-3.40 (2H, m), 3.31-3.19 (3H, m), 3.04-2.92 (1H, m), 2.80 (1H, dd), 2.68 (1H, dd), 1.48 (9H, s), 1.19 (3H, d).
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[OH:6][C:7]1[N:11]([CH3:12])[N:10]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[C:15]([CH3:23])[CH:14]=2)[CH:8]=1.[CH3:24][N:25]([CH3:28])[CH:26]=[O:27]>>[Cl:3][C:7]1[N:11]([CH3:12])[N:10]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[C:15]([CH3:23])[CH:14]=2)[C:8]=1[CH:26]=[O:27].[CH3:23][C:15]1[CH:14]=[C:13]([C:9]2[C:8]([CH:7]=[O:6])=[C:28]([Cl:3])[N:25]([CH3:24])[N:10]=2)[CH:18]=[CH:17][C:16]=1[OH:19]
Reactant: CN(C)C=O
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc(-c2cc(O)n(C)n2)ccc1OC(C)C
Product: Cc1cc(-c2nn(C)c(Cl)c2C=O)ccc1O
Product: Cc1cc(-c2nn(C)c(Cl)c2C=O)ccc1OC(C)C

Procedure:
At 0° C., to phosphorus oxychloride 43 g was added N,N-dimethylformamide 3.2 g and the resulting mixture was stirred for a half hour. Thereto was added 5-hydroxy-3-(4-isopropoxy-3-methyl-phenyl)-1-methyl-1H-pyrazole (described in Reference preparation example 95) 8.3 g. The resulting mixture was stirred at 100° C. for ten hours and the reaction solvent was distilled off under reduced pressure. To the reaction mixture was added ice water 100 ml and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and were dried over anhydrous magnesium sulfate, and was then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 5-chloro-4-formyl-3-(4-isopropoxy-3-methyl-phenyl)-1-methyl-1H-pyrazole 5.1 g and 2-methyl-4-(5-chloro-4-formyl-1-methyl-1H-pyrazol-3-yl)-phenol 0.6 g.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Br:21][C:22]([CH3:27])([CH3:26])[C:23](Br)=[O:24].C(Cl)(Cl)Cl.O>C1COCC1>[C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:23](=[O:24])[C:22]([Br:21])([CH3:27])[CH3:26])=[CH:15][CH:16]=1)([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2]
Reactant: CC(C)(Br)C(=O)Br
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(N)cc1)C(=O)O
Solvent: C1CCOC1
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(NC(=O)C(C)(C)Br)cc1)C(=O)O
Reaction time: 0.17 h
Yield: 65 %

Procedure:
Commercially available N-Boc 4-aminophenylalanine (3.62 g, 0.01447 mol) was dissolved in 50 mL of dry THF. 2-bromoisobutyryl bromide (1.757 mL, 0.01422 mol) was added dropwise over 30-60 seconds with vigorous stirring. The reaction was complete after 10 min (monitored by TLC). After approximately 20 min. the entire reaction mixture (including newly formed precipitate) was transferred to a separatory funnel with CHCl3, and approximately 100 mL of H2O. The reaction mixture was extracted with CHCl3 (3×50 mL). The organic phase was washed with distilled water (2×50 mL) and brine (50 mL). The organic phase was dried with MgSO4 and evaporated in vacuo to obtain the crude product (4.55 g). The crude solid product was recrystallized in 20-30 mL acetonitrile three times to purify the product. After three recrystallizations, N-Boc-4-(2′-bromoisobutyramido)phenylalanine was obtained in 65% yield (3.63 g). 1H NMR (500 MHz, DMSO): δ9.4 (s, 1H, COOH), δ7.8 (s, 1H, NH), δ7.5 (d, 2H, Ar H), δ7.1 (d, 2H, Ar H), δ6.0 (d, 1H, NH), δ4.2 (d, 1H, CH), δ3.05 (dd, 2H, CH2), δ2.0 (s, 6H, CH3), δ1.3 (s, 9H, CH3).
Reaction SMILES: C([C:3]1[CH:16]=[CH:15][C:6]([O:7][CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=1)=O.C(Cl)Cl.ClC1C=CC=C(C(OO)=[O:28])C=1>O>[OH:28][C:3]1[CH:16]=[CH:15][C:6]([O:7][CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=1
Reactant: CCOC(=O)C(C)Oc1ccc(C=O)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C(C)Oc1ccc(O)cc1
Yield: 52.9 %

Procedure:
A mixture of 2.2 g of ethyl 2-(4-formylphenoxy)propionate, 10 ml of methylene chloride and 2.6 g of m-chloroperbenzoic acid, were reacted for 2 hours under reflux, and after an addition of 0.5 g of water, further refluxed for 1 hour. After cooling, the reaction mixture was washed twice with 20 g of a 5% sodium hydrogen carbonate aqueous solution, then with 10 g of a 5% sodium hydrogen sulfite aqueous solution and further with 10 g of water. The mixture was concentrated by distilling off methylene chloride, and then subjected to distillation under reduced pressure, whereby 1.1 g of ethyl 2-(4-hydroxyphenoxy)propionate was obtained as a colorless transparent liquid. The boiling point was from 130° to 140° C./1 mmHg.
Reaction SMILES: [CH:1]1([C:6](Cl)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[CH3:16][O:17][C:18]1[C:32]([N+:33]([O-:35])=[O:34])=[CH:31][C:21]2[CH2:22][C@@H:23]3[C@H:28]([CH3:29])[C@:27]([CH3:30])([C:20]=2[C:19]=1[N+:36]([O-:38])=[O:37])[CH2:26][CH2:25][NH:24]3.C([O-])([O-])=O.[Na+].[Na+]>ClCCl.C(N(CC)CC)C>[CH:1]1([C:6]([N:24]2[CH2:25][CH2:26][C@:27]3([CH3:30])[C@@H:28]([CH3:29])[C@H:23]2[CH2:22][C:21]2[CH:31]=[C:32]([N+:33]([O-:35])=[O:34])[C:18]([O:17][CH3:16])=[C:19]([N+:36]([O-:38])=[O:37])[C:20]=23)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1c([N+](=O)[O-])cc2c(c1[N+](=O)[O-])[C@]1(C)CCN[C@H](C2)[C@@H]1C
Reactant: O=C(Cl)C1CCCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1c([N+](=O)[O-])cc2c(c1[N+](=O)[O-])[C@]1(C)CCN(C(=O)C3CCCC3)[C@H](C2)[C@@H]1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Cyclopentanecarbonyl chloride (0.12 g) is added to the trifluoroacetic acid salt of (2R,6R,11R)-8-methoxy-6,11-dimethyl-7,9-dinitro-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine (0.43 g) and triethylamine (0.31 mL) dissolved in dichloromethane (10 mL). The resulting solution is stirred at room temperature overnight. Then, aqueous Na2CO3 solution is added and the resulting mixture is extracted with dichloromethane. The combined extracts are washed with water and dried (Na2SO4) and the solvent is evaporated. The residue is purified by HPLC on reversed phase (MeCN/H2O) to give the product as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.CCCCCC.[CH3:19][C:20]([S:23]([N:25]=[C:26]1[CH2:29][O:28][CH2:27]1)=[O:24])([CH3:22])[CH3:21].C[Al](C)C>C1COCC1.C1(C)C=CC=CC=1>[CH3:22][C:20]([S:23]([NH:25][C:26]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:29][O:28][CH2:27]1)=[O:24])([CH3:19])[CH3:21]
Reactant: Brc1ccccn1
Reactant: CC(C)(C)S(=O)N=C1COC1
Agent: C[Al](C)C
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)(C)S(=O)NC1(c2ccccn2)COC1
Temperature: -100 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-bromopyridine (0.16 g, 1.02 mmol, 1.0 eq) in dry THF at −100° C. was slowly added a solution of n-BuLi in hexane (2.5M, 0.41 ml, 1.03 mmol, 1 eq), and reaction mixture was then kept in same temperature for 30 minute. A mixture of 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (0.18 g, 1.02 mmol, 1 eq) and a 2M solution of Me3Al (0.5 ml, 1 mmol, 1 eq) in toluene was stirred at −78° C. for 10 minutes, and then added to the above reaction mixture slowly. The reaction temperature was maintained at −100° C. for another 1 h, after which the reaction mixture warmed to 0° C. slowly. The reaction mixture was quenched with a saturated solution of Na2SO4 and extracted with ethyl acetate. The organic layer was separated and washed with a saturated brine solution, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified through a neutral alumina column using 0.5% MeOH/DCM. Yield: 0.1 g (38.5%).
Reaction SMILES: [C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].ClC(OCC(C)C)=O.CN1CCOCC1.[Br:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([NH2:40])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1>O1CCCC1.N1C=CC=CC=1>[Br:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([NH:40][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1
Reactant: Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1
Reactant: CC#CC(=O)O
Agent: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC#CC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1
Reaction time: 8 h
Yield: 55.3 %

Procedure:
A solution of 0.50 g of 2-butynoic acid in 10 ml of tetrahydrofuran was cooled in an ice bath. A 0.79 ml portion of isobutyl chloroformate followed by a 0.66 ml portion of N-methyl morpholine were added. After about 1 minute a solution of 1.6 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 10 ml of pyridine was added. The reaction was allowed to come to room temperature and stir overnight. The solvents were removed at reduced pressure and the solid was recrystallized from n-butanol to give 1.07 g of N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide: mass spectrum (m/e): 381, 383.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:10])[CH2:4][CH2:5][CH2:6][N+:7]([O-])=[O:8].[C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[CH:12]=[CH2:13].C(N(CC)CC)C.C1(N=C=O)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:10])[CH2:4][CH2:5][C:6]1[CH2:13][CH:12]([C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[O:8][N:7]=1
Reactant: COC(=O)CCC[N+](=O)[O-]
Reactant: C=CC(=O)OC(C)(C)C
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: O=C=Nc1ccccc1
Product: COC(=O)CCC1=NOC(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A solution of 105 g of 4-nitrobutyric acid methyl ester (Bruson U.S. Pat. No. 2,342,119), 64 g of t-butyl acrylate, 1 ml triethyl amine in 200 ml of toluene is stirred and treated dropwise with 137 g of phenyl isocyanate. The mixture is stirred for 72 hours at room temperature and heated at 90° C. for two hours. The mixture is cooled, filtered to remove the diphenyl urea, and concentrated under reduced pressure. The resulting oil is chromatographed on elution with hexane:ethyl-acetate; 75:25) to yield 4,5-dihydro 5-(t-butoxycarbonyl)-3-isoxazolepropanoic acid methyl ester as a colorless oil. NMR (CDCl3) and 4.87 (t, J=9 Hz, 1H), 3.70 (s, 3H), 3.20 (d, J=9 Hz, 2HO, 2.67 (s, 4H), 1.47 (s, 9H). IR (cm-1) 2970, 1740, 1600, 1556, 1445, 1396, 1373, 1340, 1300, 1262, 1230.
Reaction SMILES: CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[C@H:32]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:35][CH:34]=3)[C@@H:31]([CH2:47][CH2:48][C:49]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)=[O:50])[C:30]2=[O:58])=[CH:25][CH:24]=1.[BH4-].CSC.Cl>C1COCC1.CO>[F:22][C:23]1[CH:24]=[CH:25][C:26]([N:29]2[C@H:32]([C:33]3[CH:34]=[CH:35][C:36]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:37][CH:38]=3)[C@@H:31]([CH2:47][CH2:48][C@@H:49]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[OH:50])[C:30]2=[O:58])=[CH:27][CH:28]=1
Reactant: O=C(CC[C@H]1C(=O)N(c2ccc(F)cc2)[C@@H]1c1ccc(OCc2ccccc2)cc1)c1ccc(F)cc1
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Agent: Cl
Agent: [BH4-]
Solvent: CO
Solvent: CSC
Solvent: C1CCOC1
Product: O=C1[C@H](CC[C@H](O)c2ccc(F)cc2)[C@@H](c2ccc(OCc3ccccc3)cc2)N1c1ccc(F)cc1
Temperature: -20 °C
Reaction time: 0.08 h

Procedure:
Add (R)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c]-[1,3,2]oxazaborole (120 mg, 0.43 mmol) to 1-(4-fluorophenyl)-3(R)-(3-(4-fluorophenyl)-3-oxopropyl)-4(S)-(4-benzyloxyphenyl)-2-azetidinone (0.95 g, 1.91 mmol) in THF (3 mL) and cool to -20° C. After 5 min., add borohydride-dimethylsulfide complex (2M in THF, 0.85 mL, 1.7 mmol) dropwise over 0.5 h. After a total of 1.5 h, add CH3OH followed by HCl (1N) and extract the reaction mixture with EtOAc to obtain 1-(4-fluorophenyl)-3(R)-(3(S)-(4-fluorophenyl)-3-hydroxypropyl)-4(S)-(4-benzyloxyphenyl)-2-azetidinone.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11](=[O:25])[NH:12][C:13]2[CH:18]=[C:17]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)[CH:16]=[CH:15][C:14]=2[NH2:24])[CH:6]=1)(=O)C.C(N(CC)CC)C>CO>[NH2:24][C:14]1[CH:15]=[CH:16][C:17]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)=[CH:18][C:13]=1[NH:12][C:11](=[O:25])[C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([OH:4])[CH:6]=1
Reactant: CC(=O)Oc1cccc(C(=O)Nc2cc(-c3cccs3)ccc2N)c1
Solvent: CCN(CC)CC
Solvent: CO
Product: Nc1ccc(-c2cccs2)cc1NC(=O)c1cccc(O)c1
Temperature: 25 °C
Reaction time: 19 h
Yield: 91.9 %

Procedure:
A suspension of acetate 296 (349 mg, 0.99 mmol) in dry MeOH (6 mL) was treated with triethyl amine (1.5 mL) and stirred at room temperature for 19 h, concentrated under reduced pressure and triturated with diethyl ether to provide the title compound 297 (282.5 mg, 92% yield).
Reaction SMILES: C1(S([N:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]([O:21]C)=[O:20])=[CH:16][CH:17]=3)[C:12]([CH2:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH:31]=[C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:29][CH2:28]3)=[CH:11]2)(=O)=O)C=CC=CC=1.[OH-].[K+]>O.C(O)C>[C:33]1([C:30]2[CH2:31][CH2:32][N:27]([CH2:26][CH2:25][CH2:24][CH2:23][C:12]3[C:13]4[C:18](=[CH:17][CH:16]=[C:15]([C:19]([OH:21])=[O:20])[CH:14]=4)[NH:10][CH:11]=3)[CH2:28][CH:29]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: COC(=O)c1ccc2c(c1)c(CCCCN1CC=C(c3ccccc3)CC1)cn2S(=O)(=O)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)c1ccc2[nH]cc(CCCCN3CC=C(c4ccccc4)CC3)c2c1

Procedure:
4.68 g of methyl 1-benzenesulfonyl-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-butyl]-indole-5-carboxylate [obtainable from methyl 1-benzenesulfonyl-3-(4-chlorobutyl)-indole-5-carboxylate and 4-phenyl-1,2,3,6-tetrahydropyridine] are boiled with 1 g of KOH in 7 ml of water and 14 ml of ethanol for 16 hours, and the mixture is concentrated and worked up in the customary manner to give 3-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-butyl]-indole-5-carboxylic acid, m.p. 284°-285°.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.B([O-])([O-])O[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][CH3:44])=[C:37]([O:45][CH2:46][CH2:47][CH3:48])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>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.C1(C)C=CC=CC=1>[CH2:46]([O:45][C:37]1[CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][C:5]3[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]([CH3:31])[CH:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[CH:21][CH:22]=4)=[O:15])=[CH:7][C:6]=3[CH:32]=2)[CH:40]=[CH:39][C:38]=1[O:41][CH2:42][CH2:43][CH3:44])[CH2:47][CH3:48]
Reactant: CCCOc1ccc(OB([O-])[O-])cc1OCCC
Reactant: CN(Cc1ccc(NC(=O)C2=Cc3cc(Br)ccc3S(=O)(=O)CC2)cc1)C1CCOCC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCS3(=O)=O)cc1OCCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 73.9 %

Procedure:
A mixture of 7-bromo-N-(4-((N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (0.3 g), 3,4-dipropoxyphenyl borate (0.17 g), 1M potassium carbonate solution (1.3 ml), ethanol (1.3 ml) and toluene (25 ml) was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakis(triphenylphosphine)palladium (0.03 g), and the mixture was refluxed under argon atmosphere for 6 hours and extracted with ethyl acetate. The organic layer washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethanol to give 7-(3,4-dipropoxyphenyl)-N-(4-((N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 155) (0.27 g) as colorless crystals.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]=[CH:16][N:17]=1)=[CH:9]2)([O-])=O.O1CCCC1.O.NN>O.O.O.O.O.O.[Fe](Cl)(Cl)Cl.CO>[S:14]1[CH:15]=[CH:16][N:17]=[C:13]1[C:10]1[NH:11][C:12]2[C:8]([CH:9]=1)=[CH:7][CH:6]=[CH:5][C:4]=2[NH2:1]
Reactant: O=[N+]([O-])c1cccc2cc(-c3nccs3)[nH]c12
Agent: Cl[Fe](Cl)Cl
Agent: NN
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Nc1cccc2cc(-c3nccs3)[nH]c12
Yield: 90.7 %

Procedure:
A mixture of 7-nitro-2-(1,3-thiazol-2-yl)-1H-indole (2.21 g), iron(III) chloride hexahydrate (0.12 g), activated carbon (1.20 g), tetrahydrofuran (10 mL) and methanol (10 mL) was heated under reflux for 20 min. To the reaction mixture was added hydrazine monohydrate (2.70 g) over 15 min while heating under reflux. The reaction mixture was heated under reflux for 2 hr, filtrated, and the filtrate was concentrated. The residue was dissolved in ethyl acetate, washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography and the title compound (1.76 g, yield 90%) was obtained as yellow crystals from a fraction eluted with ethyl acetate-hexane (1:2, volume ratio). melting point 173-174° C.