Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[O:11][C:12]([NH:14][C:15]([CH3:29])([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=1)=[O:13])[CH2:8]2.O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C.Cl.[N:64]1[CH:69]=[CH:68][N:67]=[CH:66][C:65]=1[CH2:70][CH2:71][NH2:72]>C(OCC)(=O)C.O>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([CH2:16][C:15]([NH:14][C:12](=[O:13])[O:11][CH:2]2[CH:1]3[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][CH:3]2[CH2:4]4)[CH2:8]3)([CH3:29])[C:26](=[O:27])[NH:72][CH2:71][CH2:70][C:65]2[CH:66]=[N:67][CH:68]=[CH:69][N:64]=2)=[CH:18]1
Reactant: CC(Cc1c[nH]c2ccccc12)(NC(=O)OC1C2CC3CC(C2)CC1C3)C(=O)O
Reactant: NCCc1cnccn1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(Cc1c[nH]c2ccccc12)(NC(=O)OC1C2CC3CC(C2)CC1C3)C(=O)NCCc1cnccn1
Reaction time: 1.75 h
Yield: 63.2 %

Procedure:
A room temperature solution of 0.40 g (1.01 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.15 g (1.11 mmol) of 1-hydroxybenzotriazole hydrate in 15 mL of anhydrous ethyl acetate under N2 atmosphere was treated with 0.23 g (1.11 mmol) of 1,3-dicyclohexylcarbodiimide in one portion. The reaction was stirred for 1.75 hours and treated with 0.12 g (1.22 mmol) of triethylamine and 0.17 g (1.07 mmol) of 2-pyrazineethaneamine hydrochloride. The reaction as stirred for 1.75 hours and filtered. The filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was treated with 1,2-dimethoxyethane (5 mL), allowed to stand at 0°-5° C. for 16 hours, filtered, and concentrated in vacuo. Chromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil upon solvent removal. The residue was dissolved in methanol (10 mL) and water (1 mL) and concentrated in vacuo until a solid formed. The solid was suspended in water, filtered, and dried to give 0.32 g (63%) of the desired product as a white solid; mp 97°-101° C.; 1H NMR (CDCl3) δ1.4-2.0 (17H, m), 2.87 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46 (1H, d, J 15 Hz), 3.62 (2H, m), 4.74 (1H, br s), 5.23 (1H, br s), 6.95 (2H, br s), 7.0-7.2 (2H, m), 7.33 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.20 (1H, br s), 8.37 (2H, s), 8.38 (1H, s).
Reaction SMILES: [CH3:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][C:7](=O)[C:6]=2[CH:5]=[C:4]([CH3:13])[C:3]=1[NH:14][C:15](=[O:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18].[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.CC1C=CC(S(O)(=O)=O)=CC=1.C([BH3-])#N.[Na+]>C1(C)C=CC=C(C)C=1>[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][CH:7]2[CH2:8][CH2:9][CH2:10][C:11]3[C:2]([CH3:1])=[C:3]([NH:14][C:15](=[O:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:4]([CH3:13])=[CH:5][C:6]2=3)=[CH:25][CH:24]=1
Reactant: Cc1cc2c(c(C)c1NC(=O)CC(C)(C)C)CCCC2=O
Reactant: Nc1ccc(F)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: Cc1cccc(C)c1
Product: Cc1cc2c(c(C)c1NC(=O)CC(C)(C)C)CCCC2Nc1ccc(F)cc1
Temperature: 160 °C
Reaction time: 2 h
Yield: 37.7 %

Procedure:
A mixture of N-(1,3-dimethyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-3,3-dimethylbutanamide (150 mg, 0.52 mmol), 4-fluoroaniline (116 mg, 1.04 mmol), and pTSA (20 mg) in 20 ml of m-xylene was heated at 160° C. for 6 hours. The solvent was removed in vacuo, and the residue was dissolved in a mixture of methanol (10 ml) and acetic acid (2 ml). Sodium cyanoborohydride (49 mg, 0.78 mmol) was added, and the resulting mixture was stirred at room temperature for 2 hours. After neutralization with saturated sodium bicarbonate, the mixture was extracted with chloroform (×3). The organic layer were combined, dried over anhydrous Na2SO4 and evaporated to dryness in vacuo. The residue was purified by Biotage (hexane/EtOAc, 0-30%, 40 min) to give a white solid (75 mg, 38%). 1H-NMR δ (DMSO-d6, 500 MHz): 9.09 (brs, 1H, exchangeable with D2O), 7.00 (s, 1H), 6.89 (t, J=7.5 Hz, 2H), 6.65 (dd, J=5.7 and 7.5 Hz, 2H), 5.70 (brs, 1H, exchangeable with D2O), 4.45 (m, 1H), 2.61 (m, 1H), 2.51 (m, 1H), 2.20 (s, 2H), 2.06 (s, 3H), 1.99 (s, 3H), 1.84 (m, 1H), 1.73 (m, 3H), 1.04 (s, 9H). MS: 383 (M+1).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:8](=[O:17])[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:3][CH2:2]1.Cl[C:19]1[N:24]=[CH:23][N:22]=[C:21]([C:25]([C:27]2[CH:37]=[C:36]([CH3:38])[C:30]3[N:31]([CH3:35])[C:32](=[O:34])[O:33][C:29]=3[CH:28]=2)=[O:26])[CH:20]=1.CCN(C(C)C)C(C)C.O>CN(C=O)C>[CH3:35][N:31]1[C:30]2[C:36]([CH3:38])=[CH:37][C:27]([C:25]([C:21]3[N:22]=[CH:23][N:24]=[C:19]([N:1]4[CH2:2][CH2:3][CH:4]([C:7]5[C:8](=[O:17])[NH:9][C:10]6[C:15]([CH:16]=5)=[CH:14][CH:13]=[CH:12][CH:11]=6)[CH2:5][CH2:6]4)[CH:20]=3)=[O:26])=[CH:28][C:29]=2[O:33][C:32]1=[O:34]
Reactant: Cc1cc(C(=O)c2cc(Cl)ncn2)cc2oc(=O)n(C)c12
Reactant: O=c1[nH]c2ccccc2cc1C1CCNCC1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)c2cc(N3CCC(c4cc5ccccc5[nH]c4=O)CC3)ncn2)cc2oc(=O)n(C)c12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
60 mg (0.26 mmol) 3-piperidin-4-yl-1H-quinolin-2-one, 80 mg (0.26 mmol) 6-(6-chloropyrimidine-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one and 0.15 mL (0.86 mmol) DIPEA were combined in 3 mL DMF and stirred overnight at RT. The reaction mixture was added to water and the precipitate formed was suction filtered, washed with MeOH and dried.
Reaction SMILES: CON(C)[C:4](=[O:28])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[CH:12]=[CH:13][C:14]3[O:18][C:17]([CH2:19][CH2:20][N:21]4[CH2:25][CH2:24][CH2:23][C@H:22]4[CH3:26])=[CH:16][C:15]=3[CH:27]=2)[CH:6]=1.[CH:30]1([Mg]Br)[CH2:32][CH2:31]1>>[CH:30]1([C:4]([C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([C:11]3[CH:12]=[CH:13][C:14]4[O:18][C:17]([CH2:19][CH2:20][N:21]5[CH2:25][CH2:24][CH2:23][C@H:22]5[CH3:26])=[CH:16][C:15]=4[CH:27]=3)[CH:6]=2)=[O:28])[CH2:32][CH2:31]1
Reactant: CON(C)C(=O)c1cccc(-c2ccc3oc(CCN4CCC[C@H]4C)cc3c2)c1
Reactant: Br[Mg]C1CC1
Product: C[C@@H]1CCCN1CCc1cc2cc(-c3cccc(C(=O)C4CC4)c3)ccc2o1
Yield: 48 %

Procedure:
The product from Example 145 and cyclopropylmagnesium bromide were processed as described in Example 146 to provide the title compound (48% yield). MS (ESI APCI) m/z 374 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.08-1.22 (m, 7H), 1.39-1.53 (m, 1H), 1.73-1.86 (m, 2H), 1.95-2.08 (m, 1H), 2.23-2.35 (m, 1H), 2.41-2.60 (m, 2H), 2.87-3.15 (m, 3H), 3.19-3.35 (m, 2H), 6.63 (s, 1H), 7.48-7.55 (m, 2H), 7.60 (dd, 1H), 7.78-7.81 (m, 1H), 7.89 (ddd, 1H), 8.02 (ddd, 1H), 8.25 (dd, 1H).
Reaction SMILES: [CH2:1]([C:4]1[C:13]2[O:12][C:11]([C:14]3[NH:18][N:17]=[N:16][N:15]=3)=[CH:10][C:9](=[O:19])[C:8]=2[C:7]([O:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:6][CH:5]=1)[CH:2]=[CH2:3].C(=O)(O)[O-:27].[Na+].[N+]([O-])([O-])=[O:32].[Ca+2:35].[N+]([O-])([O-])=[O:37]>O>[CH2:1]([C:4]1[C:13]2[O:12][C:11]([C:14]3[NH:15][N:16]=[N:17][N:18]=3)=[CH:10][C:9](=[O:19])[C:8]=2[C:7]([O:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:6][CH:5]=1)[CH:2]=[CH2:3].[OH2:27].[OH2:32].[OH2:37].[OH2:12].[OH2:12].[Ca:35]
Reactant: O=C([O-])O
Reactant: [Ca+2]
Reactant: O=[N+]([O-])[O-]
Agent: C=CCc1ccc(OCCC(C)C)c2c(=O)cc(-c3nnn[nH]3)oc12
Agent: [Na+]
Solvent: O
Product: [Ca]

Procedure:
5Parts of 5-[8-allyl-5-(3-methylbutoxy)-4-oxo-4H-1-benzopyran-2-yl]tetrazole and 1.29 parts of sodium bicarbonate were mutually dissolved in 200 parts of water. To this stirred solution 1.25 parts of calcium nitrate in 100 parts of water were added. A creamy precipitate was produced. The mixture was cooled and the precipitate was collected. The compound was finely powdered, treated with boiling water, collected and dried in vacuo. 4.8 Parts of 5-[8-allyl-5-(3-methylbutoxy)-4-oxo-4H-1-benzopyran-2-yl]tetrazole as its calcium salt pentahydrate were obtained.
Reaction SMILES: F[B-](F)(F)F.C[N+](C)=C(N(C)C)ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[C:30]([C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[C:47]3[C:46](=[O:48])[CH2:45][CH2:44][CH2:43][C:42]=3[N:41]([C:49]3[CH:54]=[CH:53][CH:52]=[C:51]([C:55]([F:58])([F:57])[F:56])[CH:50]=3)[C:40](=[O:59])[N:39]2[CH2:60][C:61]([OH:63])=O)=[CH:34][CH:33]=1)#[N:31].[CH3:64][N:65]1[C:69]2[CH2:70][NH:71][CH2:72][C:68]=2[CH:67]=[N:66]1>CN(C)C=O>[CH3:64][N:65]1[C:69]2[CH2:70][N:71]([C:61](=[O:63])[CH2:60][N:39]3[CH:38]([C:35]4[CH:34]=[CH:33][C:32]([C:30]#[N:31])=[CH:37][CH:36]=4)[C:47]4[C:46](=[O:48])[CH2:45][CH2:44][CH2:43][C:42]=4[N:41]([C:49]4[CH:54]=[CH:53][CH:52]=[C:51]([C:55]([F:57])([F:56])[F:58])[CH:50]=4)[C:40]3=[O:59])[CH2:72][C:68]=2[CH:67]=[N:66]1
Reactant: N#Cc1ccc(C2C3=C(CCCC3=O)N(c3cccc(C(F)(F)F)c3)C(=O)N2CC(=O)O)cc1
Reactant: Cn1ncc2c1CNC2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1ncc2c1CN(C(=O)CN1C(=O)N(c3cccc(C(F)(F)F)c3)C3=C(C(=O)CCC3)C1c1ccc(C#N)cc1)C2

Procedure:
N,N,N′,N′-Tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (161 mg, 0.50 mmol) and triethylamine (210 μL, 1.51 mmol) are added to a mixture of 2-(4-(4-cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazolin-3(4H)-yl)acetic acid (example 32, 235 mg, 0.50 mmol) in N,N-dimethylform-amide (2 mL). After 5 min a solution of 1-methyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole (123 mg, 1.00 mmol) in N,N-dimethylformamide (3 mL) is added, and the mixture is stirred over night and purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3). Yield: 86 mg; ESI mass spectrum [M+H]+=575; Retention time HPLC: 0.86 min (Z011_S03).
Reaction SMILES: C(OCCCCC[CH:10]([O:17][C:18]1[CH:35]=[CH:34][C:33]2[C@@H:32]3[C@H:23]([C@H:24]4[C@@:28]([CH2:30][CH2:31]3)([CH3:29])[C:27](=[O:36])[CH2:26][CH2:25]4)[CH2:22][CH2:21][C:20]=2[CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=O)C.[OH-].[Na+].Cl.C([O:43][CH2:44][CH3:45])(=O)C.O1C[CH2:49][CH2:48][CH2:47]1>CO>[CH2:10]([O:17][C:18]1[CH:35]=[CH:34][C:33]2[C@@H:32]3[C@H:23]([C@H:24]4[C@@:28]([CH2:30][CH2:31]3)([CH3:29])[C:27](=[O:36])[CH2:26][CH2:25]4)[C@H:22]([CH2:47][CH2:48][CH2:49][CH2:45][CH2:44][OH:43])[CH2:21][C:20]=2[CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C1CCOC1
Reactant: CCOC(C)=O
Reactant: CC(=O)OCCCCCC(Oc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@]12CC[C@@H]3c4ccc(OCc5ccccc5)cc4C[C@@H](CCCCCO)[C@H]3[C@@H]1CCC2=O

Procedure:
A solution of 7.26 g of α-(5-acetoxypentyl)-3-benzyloxy-estra-1,3,5(10)-trien-17-one in 80 ml of methanol and 3 ml of tetrahydrofuran is saponified with 22.2 ml of 2N sodium hydroxide solution overnight at room temperature. The reaction solution is poured into 2N hydrochloric acid, shaken out with ethyl acetate, the organic phase is washed with saturated common salt solution, dried on sodium sulfate and concentrated by evaporation. 6.7 g of 3-benzyloxy-7α-(5-hydroxypentyl)-estra-1,3,5(10)-trien-17-one is obtained as foam.
Reaction SMILES: [C:1]1([O-:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+].[Cl:9][C:10](Cl)=[CH:11][C:12]1([CH2:17][CH3:18])[CH2:16][CH2:15][CH2:14][CH2:13]1>CN1CCCC1=O.C(Cl)Cl>[Cl:9][CH:10]=[C:11]([C:12]1([CH2:17][CH3:18])[CH2:16][CH2:15][CH2:14][CH2:13]1)[O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [O-]c1ccccc1
Reactant: CCC1(C=C(Cl)Cl)CCCC1
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: ClCCl
Product: CCC1(C(=CCl)Oc2ccccc2)CCCC1
Temperature: 210 °C
Yield: 87.7 %

Procedure:
140 g (4.2 mol) of sodium phenolate in 500 ml of N-methylpyrrolidone were heated to 200° C. 116 g (0.6 mol) of 1-(2,2-dichlorovinyl)-1-ethyl-cyclopentane were added dropwise so slowly that the reaction temperature did not fall below 195° C. The mixture was then stirred for a further hour at 210° C. After the mixture had cooled, it was diluted with methylene chloride and extracted several times by shaking with 2N sodium hydroxide solution. The organic phase, which had been dried over sodium sulphate, was concentrated in vacuo, and the residue was fractionated. 132 g (88% of theory) of 1-chloro-2-(1-ethylcyclopentyl)-2-phenoxy-ethylene of boiling point 115° to 125° C./0.1 mm Hg were obtained. ##STR21##
Reaction SMILES: C(OC([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][O:15][C:16]2[CH:25]=[CH:24][C:23]3[C:22](=[O:26])[CH2:21][CH2:20][CH2:19][C:18]=3[CH:17]=2)[N:10]=[CH:9]1)=O)(C)(C)C.[Br:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1>[OH-].[K+].CCO>[Br:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[C:21]2[CH2:20][CH2:19][C:18]3[C:23](=[CH:24][CH:25]=[C:16]([O:15][CH2:14][CH2:13][C:11]4[N:10]=[CH:9][NH:8][CH:12]=4)[CH:17]=3)[C:22]2=[O:26])=[CH:30][CH:29]=1
Reactant: CC(C)(C)OC(=O)n1cnc(CCOc2ccc3c(c2)CCCC3=O)c1
Reactant: O=Cc1ccc(Br)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C1C(=Cc2ccc(Br)cc2)CCc2cc(OCCc3c[nH]cn3)ccc21
Yield: 52.4 %

Procedure:
According to the method of Example 32, 4-[2-(5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-ethyl]-imidazole-1-carboxylic acid tert-butyl ester (0.278 g, 0.78 mmol) was reacted with p-bromobenzaldehyde (0.217 g, 1.17 mmol) in 5 mL of 4% KOH in EtOH overnight to afford 0.173 g (51%) of the title compound as a dark cream-colored powder, mp 176-178° C.: CI-MS m/e 423, 425 M++1).
Reaction SMILES: [Li]C(C)(C)C.Br[C:7]1[CH:8]=[C:9]([CH:18]=[C:19]([F:21])[CH:20]=1)[O:10][Si](C(C)(C)C)(C)C.[CH3:22][N:23]([CH2:25][CH:26]1[CH2:32][CH2:31][CH:30]2[CH:28]([CH2:29]2)[C:27]1=[O:33])[CH3:24].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(Cl)Cl>[CH3:24][N:23]([CH2:25][CH:26]1[CH2:32][CH2:31][CH:30]2[CH:28]([CH2:29]2)[C:27]1([C:7]1[CH:8]=[C:9]([OH:10])[CH:18]=[C:19]([F:21])[CH:20]=1)[OH:33])[CH3:22]
Reactant: CN(C)CC1CCC2CC2C1=O
Reactant: CC(C)(C)[Si](C)(C)Oc1cc(F)cc(Br)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN(C)CC1CCC2CC2C1(O)c1cc(O)cc(F)c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 13.9 %

Procedure:
Add a solution of t-BuLi (19.4 mL, 25.2 mmol) via syringe to a solution of (3-bromo-5-fluoro-phenoxy)-tert-butyl-dimethyl-silane (6.99 g, 22.9 mmol) in THF (100 mL) at −78° C. under N2. After being stirred at −78° C. for 1 hour, add dropwise a solution of 3-dimethylaminomethyl-bicyclo[4.1.0]heptan-2-one (2.55 g, 15.3 mmol) to the reaction mixture and stir the reaction mixture at −78° C. for additional 2 hours. Quench the reaction with saturated NH4Cl solution (30 mL). Extract the resultant aqueous mixture with EtOAc (100 mL×3). The combined organic layers are washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Treat the residue with TBAF (6.00 g, 22.9 mmol) in CH2Cl2 (80 mL) at ambient temperature for 4 hours. Concentrate the mixture, and purify the residue by preparative HPLC to give 3-dimethylaminomethyl-2-(3-fluoro-5-hydroxy-phenyl)-bicyclo[4.1.0]heptan-2-ol as white solid (592 mg, yield: 13.9%). MS (m/z): 280 (M+1).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3S[N:8]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-:17].[K+].[K+].Cl[CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=1[O:36][CH3:37]>[I-].[K+].C(#N)C>[O:17]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:7]([CH:4]2[CH2:5][CH2:6][N:1]([CH2:23][CH2:24][CH2:25][O:26][C:27]3[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=3[O:36][CH3:37])[CH2:2][CH2:3]2)=[N:8]1
Reactant: O=C([O-])[O-]
Reactant: COc1cc(C(C)=O)ccc1OCCCCl
Reactant: c1ccc2c(C3CCNCC3)nsc2c1
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: COc1cc(C(C)=O)ccc1OCCCN1CCC(c2noc3ccccc23)CC1
Yield: 109 %

Procedure:
A mixture of 3-(4-piperidinyl)-1,2-benzisothiazole (3.0 g, 13.7 mmol), potassium carbonate (2.3 g, 16.5 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (4.0 g, 16.5 mmol), potassium iodide (200 mg) and acetonitrile (100 ml) was stirred at reflux under N2 for 24 hours. The cooled reaction was filtered and the cake was washed well with acetonitrile. The filtrate was concentrated to an oily residue, which was partitioned between water and ethyl acetate. The ethyl acetate extract was washed well with water, dried with MgSO4 and concentrated to yield 6.1 g of a beige oil which solidified upon standing. The product was triturated with diethyl ether and filtered to give 4.2 g of a beige solid. The compound was recrystallized from ethyl alcohol to afford 3.5 g, and another recrystallization from ethyl alcohol (utilizing decolonizing carbon) provided 2.4 g (41%) of 1-[4-[3-[4-(1,2-benzisothiazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone, m.p. 93°-95° C.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1([CH2:17][CH3:18])[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:16].[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1>>[ClH:1].[CH2:17]([C:6]1([CH2:5][CH2:4][CH2:3][CH2:2][N:29]2[CH2:28][CH2:27][N:26]([C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][CH:24]=3)[CH2:31][CH2:30]2)[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:16])[CH3:18]
Reactant: Fc1ccc(N2CCNCC2)cc1
Reactant: CCC1(CCCCCl)C(=O)Nc2cc(F)ccc21
Product: CCC1(CCCCN2CCN(c3ccc(F)cc3)CC2)C(=O)Nc2cc(F)ccc21
Product: Cl

Procedure:
The title compound is prepared according to process H using processing method 2 from 3-(4-chlorobutyl)-3-ethyl-6-fluoro-1,3-dihydro-2H-indol-2-one and 1-(4-fluorophenyl)-piperazine.