Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC(=O)NC(C(N1C(C2NC(C3C=CC4C(=CC=C(C5C=CC(C6NC(C7C8CC(CC8)N7C(=O)C(NC(OC)=O)C(C)C)=NC=6)=CC=5)C=4)C=3)=CN=2)CC2(CC2)C1)=O)C(C)C.[CH3:63][O:64][C:65](=[O:104])[NH:66][CH:67]([C:71]([N:73]1[CH:78]([C:79]2[NH:80][C:81]([C:84]3[CH:93]=[CH:92][C:91]4[C:86](=[CH:87][CH:88]=[C:89](B5OC(C)(C)C(C)(C)O5)[CH:90]=4)[CH:85]=3)=[CH:82][N:83]=2)[CH:77]2[CH2:103][CH:74]1[CH2:75][CH2:76]2)=[O:72])[CH:68]([CH3:70])[CH3:69].[C:105]([O:109][C:110]([N:112]1[CH:118]([C:119]2[NH:120][C:121]([C:124]3[CH:129]=[CH:128][C:127](Br)=[CH:126][CH:125]=3)=[CH:122][N:123]=2)[CH2:117][C:114]2([CH2:116][CH2:115]2)[CH2:113]1)=[O:111])([CH3:108])([CH3:107])[CH3:106].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C>[C:105]([O:109][C:110]([N:112]1[CH:118]([C:119]2[NH:120][C:121]([C:124]3[CH:129]=[CH:128][C:127]([C:89]4[CH:88]=[CH:87][C:86]5[C:91](=[CH:92][CH:93]=[C:84]([C:81]6[NH:80][C:79]([CH:78]7[CH:77]8[CH2:103][CH:74]([CH2:75][CH2:76]8)[N:73]7[C:71](=[O:72])[CH:67]([NH:66][C:65]([O:64][CH3:63])=[O:104])[CH:68]([CH3:70])[CH3:69])=[N:83][CH:82]=6)[CH:85]=5)[CH:90]=4)=[CH:126][CH:125]=3)=[CH:122][N:123]=2)[CH2:117][C:114]2([CH2:116][CH2:115]2)[CH2:113]1)=[O:111])([CH3:108])([CH3:107])[CH3:106]
Reactant: CC(C)(C)OC(=O)N1CC2(CC2)CC1c1ncc(-c2ccc(Br)cc2)[nH]1
Reactant: COC(=O)NC(C(=O)N1C2CCC(C2)C1c1ncc(-c2ccc3cc(B4OC(C)(C)C(C)(C)O4)ccc3c2)[nH]1)C(C)C
Agent: COC(=O)NC(C(=O)N1CC2(CC2)CC1c1ncc(-c2ccc3cc(-c4ccc(-c5cnc(C6C7CCC(C7)N6C(=O)C(NC(=O)OC)C(C)C)[nH]5)cc4)ccc3c2)[nH]1)C(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: COC(=O)NC(C(=O)N1C2CCC(C2)C1c1ncc(-c2ccc3cc(-c4ccc(-c5cnc(C6CC7(CC7)CN6C(=O)OC(C)(C)C)[nH]5)cc4)ccc3c2)[nH]1)C(C)C
Yield: 59.5 %

Procedure:
This compound was prepared using the procedure used to prepare [1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo [2.2.1]hept-3-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (example EZ) using [2-Methyl-1-(3-{5-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carbonyl)-propyl]-carbamic acid methyl ester (2.25 mmol), 6-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (2.39 mmol), and potassium carbonate (2M, 4.3 mL, 8.55 mmol). The reaction was performed under an argon atmosphere. The crude reaction was diluted in ethyl acetate, washed with water and purified by normal phase silica chromatography (50-100% Hexanes:EthylAcetate+10% Methanol). 6-{5-[4-(6-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (1.05 g, 60%) was obtained as a tan solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([S:12]([NH2:15])(=[O:14])=[O:13])=[CH:8][C:4]=1[C:5]([OH:7])=O.[CH2:16]([N:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[CH2:23][NH2:24])[CH3:17].C1C(=O)N(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)C(=O)C1.C(N(CC)CC)C>C(#N)C>[CH3:17][CH2:16][N:18]1[CH:19]([CH2:23][NH:24][C:5]([C:4]2[CH:8]=[C:9]([S:12]([NH2:15])(=[O:14])=[O:13])[CH:10]=[CH:11][C:3]=2[O:2][CH3:1])=[O:7])[CH2:20][CH2:21][CH2:22]1
Reactant: COc1ccc(S(N)(=O)=O)cc1C(=O)O
Reactant: CCn1cccc1CN
Agent: O=C1CCC(=O)N1OP(=O)(Oc1ccccc1)Oc1ccccc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCN1CCCC1CNC(=O)c1cc(S(N)(=O)=O)ccc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 24 %

Procedure:
A solution of 462 mg (0.002 mol) of 2-methoxy-5-aminosulfonylbenzoic acid and 256 mg (0.002 mol) of N-ethyl-2-aminomethylpyrrole in 10 ml of acetonitrile was admixed with 694 mg (0.002 mol) of SDPP and 202 mg (0.002 mol) of triethylamine, and the admixture was stirred overnight at room temperature. The crystalline material deposited was collected by filtration and washed with acetonitrile and then with ethanol to give sulpiride, that is, 5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoxybenzamide. mp. 182°~185° C. Yield 24%.
Reaction SMILES: CN(C)P(N(C)C)N(C)C.Br[C:12](Br)([F:14])[F:13].[CH3:16][C:17]([CH3:37])([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:24]=1)[CH:18]=O.C(OCC)C>COCCOCCOCCOC>[CH3:16][C:17]([CH3:37])([CH:18]=[C:12]([F:14])[F:13])[CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:24]=1
Reactant: CC(C)(C=O)COCc1ccc(F)c(Oc2ccccc2)c1
Reactant: FC(F)(Br)Br
Agent: CN(C)P(N(C)C)N(C)C
Solvent: COCCOCCOCCOC
Solvent: CCOCC
Product: CC(C)(C=C(F)F)COCc1ccc(F)c(Oc2ccccc2)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 13.5 %

Procedure:
Hexamethylphosphorous triamide (0.65 g) was added portionwise to a stirred solution of dibromodifluoromethane (0.42 g) in triglyme (3 cm3) whilst being maintained at 0° C. under an atmosphere of nitrogen. After a period of 10 minutes a pale yellow colouration was observed and a solution of 2,2-dimethyl-3-(4-fluoro-3-phenoxybenzyloxy)propan-1-al (0.3 g) in triglyme (2 cm3) was added. After stirring for a further two hours, whilst being maintained at 0° C., the reaction mixture was allowed to warm to the ambient temperature. When GLC examination of a worked-up portion of the reaction mixture showed an absence of further reaction, the reaction mixture was poured into diethylether and sequentially washed with water and brine. The solvent was removed by evaporation under reduced pressure to give a pale yellow liquid which was subjected to short-path distillation (boiling point 75° C./0.01 mm Hg). The residue was then subjected to column chromatography on silica gel using petroleum ether (boiling range 40°-60° C.) containing 5% by volume diethyl ether as eluent to give 2,2-dimethyl-1-(4-fluoro-3-phenoxybenzyloxy)-4,4-difluorobut-3-ene (0.045 g).
Reaction SMILES: [CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([CH:19]=[O:20])[CH:17]=[CH:18][C:4]1=2)[CH3:2].CC(=CC)C.P([O-])(O)(O)=[O:27].[Na+].Cl([O-])=O.[Na+]>O.C(O)(C)(C)C>[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([C:19]([OH:27])=[O:20])[CH:17]=[CH:18][C:4]1=2)[CH3:2]
Reactant: O=P([O-])(O)O
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(C=O)ccc21
Agent: CC=C(C)C
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: CC(C)(C)O
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(C(=O)O)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 44 %

Procedure:
To a t-butanol (20 ml) and H2O (5 ml) solution of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (2.25 g) and 2-methyl-2-butene(3.25 ml) were added sodium dihydrogenphosphate (0.92 g) and sodium chlorite (2.081 g), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure to give the title compound (0.98 g) as a white powder.
Reaction SMILES: Cl.[NH2:2][CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([CH3:6])=O.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[NH:21][C:22]#[N:23].C(N(CC)CC)C>C(O)C>[ClH:13].[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[NH:21][C:22]1[NH:2][C:3]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:4]([CH3:6])[N:23]=1
Reactant: N#CNc1c(Cl)cccc1Cl
Reactant: CC(=O)C(N)c1ccccc1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1nc(Nc2c(Cl)cccc2Cl)[nH]c1-c1ccccc1
Yield: 14.7 %

Procedure:
1-Amino-1-phenylacetone hydrochloride (189 mg), 2,6-dichlorophenylcyanamide (187 mg, prepared as described in J. Med. Chem., 1975, 18, 90-99) and triethylamine (101 mg) were kept at the reflux temperature in ethanol (10 ml) for 3 hours. Cooling was followed by drying in vacuo and purification by preparative HPLC. The product-containing fractions were combined, the acetonitrile was stripped in a rotary evaporator, and the aqueous residue was neutralized with potassium carbonate and extracted three times with ethyl acetate. Drying over magnesium sulfate was followed by evaporation to dryness and, after addition of hydrochloric acid, freeze drying. 26 mg of the title compound were obtained.
Reaction SMILES: O[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=[N+]([O-])c1ccc(-c2cc3c(O)ncnc3[nH]2)cc1
Product: O=[N+]([O-])c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1

Procedure:
4-Chloro-6-(4-nitro-phenyl)-7H-pyrrolo[2,3-d]pyrimidine is prepared, with the exclusion of moisture, by heating 4-hydroxy-6-(4-nitro-phenyl)-7H-pyrrolo[2,3-d]pyrimidine to boiling point with an excess of POCl3. The suspension is concentrated to a residual volume of 20 ml by evaporation. The residue is introduced in portions into water, neutralized with solid NaHCO3, and 0.2 liter of ethyl acetate is added. Filtration and washing with hot THF yield the title compound, m.p. >280° C.; FAB-MS: (M+H)+ =275.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[C:20]([F:23])([F:22])[F:21]>CN1C(=O)CCC1.O>[CH2:1]([O:8][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[C:20]([F:21])([F:22])[F:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1
Reactant: COc1ccc(F)c(C(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: COc1ccc(OCc2ccccc2)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
18 g (166.67 mmol) of benzylalcohol was slowly added to a solution of 6.7 g (167.50 mmol) of sodium hydride in 148 mL NMP. The reaction mixture was stirred for 30 min at RT, then a solution of 27 g (139.09 mmol) of 1-fluoro-4-methoxy-2-trifluoromethyl-benzene in 515 mL NMP was added, and this was stirred for 30 min at RT and for 2 h at 100° C. After cooling to RT the mixture was diluted with water and extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried on sodium sulphate and evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate).
Reaction SMILES: [Br:1][C:2]1[C:3]2[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][CH3:13])[C:4]=2[S:5][CH:6]=1.C([Li])CCC.[CH3:19][S:20]SC.Cl>CCCCCC.CCOCC>[CH3:19][S:20][C:6]1[S:5][C:4]2[C:7]([CH2:11][NH:12][CH3:13])=[CH:8][CH:9]=[CH:10][C:3]=2[C:2]=1[Br:1]
Reactant: CNCc1cccc2c(Br)csc12
Reactant: CSSC
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CNCc1cccc2c(Br)c(SC)sc12
Temperature: 25 °C

Procedure:
To a solution of 2.55 g of N-(3-bromo-7-benzo[b]thienylmethyl)methylamine in abs. ether are added dropwise under inert gas at -70° 13.8 ml (2 equivalents) of a 15% solution of n-butyllithium in n-hexane. 1.9 ml of dimethyldisulfide are then added slowly at -70° and the reaction mixture gradually warmed to room temperature. It is then poured into ice-cooled 2N HCl, shaken and the acid phase separated, made alkaline with NaOH and extracted with ether. The ether phase is dried, concentrated under vacuum and the oil thus obtained directly further reacted.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[N+:9]([O-])=[CH:10]2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[N:9]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc2cc(-c3ccccc3OC)[n+]([O-])cc2c1
Product: COc1ccc2cc(-c3ccccc3OC)nc(Cl)c2c1

Procedure:
7-Methoxy-3-(2-methoxyphenyl)isoquinoline-2-oxide (0.60 g) and phosphorus oxychloride (5 ml) were reacted at 110° C. for 2 hr. The reaction solution was concentrated, and to the resulting residue were added ethyl acetate and an aqueous saturated sodium bicarbonate. The resulting organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system), to give 0.56 g of the title compound as a white solid.
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:38][CH2:37][C@@:36]2([CH3:39])[C:11](=[CH:12][CH2:13][C@@H:14]3[C@@H:35]2[CH2:34][CH2:33][C@@:32]2([CH3:40])[C@H:15]3[CH2:16][CH2:17][C@@H:18]2[C@H:19]([CH3:31])[CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C:10]1([CH3:42])[CH3:41])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].BrN1C(C)(C)C(=O)N(Br)C1=O>CCCCCC.C1C=CC=CC=1>[Si:1]([O:8][C@H:9]1[CH2:38][CH2:37][C@@:36]2([CH3:39])[C:11](=[CH:12][CH:13]=[C:14]3[C@@H:35]2[CH2:34][CH2:33][C@@:32]2([CH3:40])[C@H:15]3[CH2:16][CH2:17][C@@H:18]2[C@H:19]([CH3:31])[CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:26])[CH3:25])[C:10]1([CH3:41])[CH3:42])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: C[C@H](CCCO[Si](C)(C)C(C)(C)C)[C@H]1CC[C@H]2[C@@H]3CC=C4C(C)(C)[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: CCCCCC
Solvent: c1ccccc1
Product: C[C@H](CCCO[Si](C)(C)C(C)(C)C)[C@H]1CC[C@H]2C3=CC=C4C(C)(C)[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Yield: 88.9 %

Procedure:
3β,24-Bis(tert-butyldimethylsilyloxy)-4,4-dimethylchol-5-ene (44 g) is dissolved in a warm mixture of hexane (2 l) and benzene (540 ml). 1,3-Dibromo-5,5-dimethylhydantoin (15.32 g) is added and the mixture is refluxed for 20 min and then cooled rapidly to room temperature, and the insoluble material is removed by filtration. The filtrate is concentrated under reduced pressure and o-xylene (2 l) and quinaldine (84 ml) is added. The mixture is refluxed for 1 hour. After aqueous work-up and trituration with methanol, 3β,24-bis (tert-butyldimethylsilyloxy)-4,4-dimethylchola-5,7-diene (39 g) is isolated. Melting point: 98-106° C. 1H-NMR (CDCl3, 400 MHz): δ=5.9 (1H, m); 5.54 (1H, m); 3.58 (2H, m); 3.35 (1H, m); 0.91 (18H, s); 0.05 (12H, m).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]2[O:32][CH2:33][C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][CH:40]=[N:41]3)=[CH:36][CH:35]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]2[O:32][CH2:33][C:34]2[CH:43]=[C:42]3[C:37]([CH2:38][CH2:39][CH2:40][NH:41]3)=[CH:36][CH:35]=2)=[CH:17][CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCCOCc3ccccc3)cc2)C(OCc2ccc3cccnc3c2)C1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCCOCc3ccccc3)cc2)C(OCc2ccc3c(c2)NCCC3)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 59.6 %

Procedure:
A solution of 116 mg (0.20 mmol) of tert-butyl (3RS,4RS)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-(quinolin-7-ylmethoxy)-piperidine-1-carboxylate in 1.5 ml of methanol was treated with 24 mg (0.1 mmol) of nickel(II) chloride hexahydrate and 30 mg (0.8 mmol) of sodium borohydride. The dark suspension was stirred at 0° C. for 1 hour and at room temperature for a further hour. For the working-up, the mixture was partitioned between 20 ml of ether and 5 ml of aqueous saturated ammonium chloride solution and then the organic phase was separated. The aqueous phase was extracted three times with 20 ml of ether each time. The combined ether phases were dried over magnesium sulphate and finally the solvent was distilled off under reduced pressure. The crude product (150 mg) was purified by chromatography on silica gel with a 1:1 mixture of ethyl acetate and hexane as the eluent. There were obtained 70 mg (60% of theory) of tert-butyl (3RS,4RS)-4-[4-(3-benzyloxy-propoxy)-phenyl]-3-(1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-piperidine-1-carboxylate as a light yellow resin; MS: 587 (M+H)+.
Reaction SMILES: O.NN.[CH3:4][N:5]1[C:9]([CH3:10])=[CH:8][N:7]([N:11]=CC2C=NC=CC=2)[C:6]1=[O:19]>CO>[NH2:11][N:7]1[CH:8]=[C:9]([CH3:10])[N:5]([CH3:4])[C:6]1=[O:19]
Reactant: Cc1cn(N=Cc2cccnc2)c(=O)n1C
Agent: NN
Solvent: CO
Solvent: O
Product: Cc1cn(N)c(=O)n1C

Procedure:
2 g of hydrazine hydrate are added to a solution of 2 g of 3,4-dimethyl-1-(pyridin-3-ylmethyleneamino)-2,3-dihydroimidazol-2-one in 12 ml of methanol and the suspension is boiled under reflux for 6 hours, then concentrated by evaporation and chromatographed on silica gel. 1 g of pyridine-3-carbaldehyde hydrazone and 0.7 g of the title compound having a melting point of 115-119° are thus obtained.
Reaction SMILES: [C:1]([NH:18][C@H:19]([C:23]([O:25][CH2:26][CH:27]([OH:38])[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])=[O:24])[CH:20]([CH3:22])[CH3:21])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].N1C=CC=CC=1.[C:45](Cl)(=[O:63])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62].C(=O)([O-])O.[Na+]>ClCCl>[C:1]([NH:18][C@H:19]([C:23]([O:25][CH2:26][CH:27]([O:38][C:45](=[O:63])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[C:28]([O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:29])=[O:24])[CH:20]([CH3:22])[CH3:21])([O:3][CH2:4][CH:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:2]
Reactant: CCCCCCCCCCCCCCCCCC(=O)Cl
Reactant: CC(C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OCC(O)C(=O)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCCCC(=O)OC(COC(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of benzyl 3-(N-FMOC-L-valyloxy)-2-hydroxypropionate (4.6 g 8.89 mmole) and pyridine (1.41 g, 17.8 mmole) in 80 ml dichloromethane was added dropwise a solution of stearoylchloride (3.64 g, 12 mmole) in 20 ml dichloromethane and the mixture was stirred overnight at room temperature. 100 ml of 5% sodium hydrogencarbonate solution was added and the mixture stirred for 30 minutes. The organic phase was seperated and the water phase was extracted two times with dichloromethane. The combined organic phases were dried with sodium sulfate and concentrated in vacuo. The product was isolated by silica gel chromatography. Yield: 6.1 g=87%
Reaction SMILES: [O:1]=[C:2]([N:5]1[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][O:7][C:6]1=[O:17])[CH2:3][CH3:4].[CH3:18][C@@H:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:20]=[O:21]>>[O:1]=[C:2]([N:5]1[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][O:7][C:6]1=[O:17])[C@H:3]([CH3:4])[C@H:20]([OH:21])[C@@H:19]([CH3:18])[CH2:22][O:23][Si:24]([C:27]([CH3:29])([CH3:28])[CH3:30])([CH3:25])[CH3:26]
Reactant: C[C@H](C=O)CO[Si](C)(C)C(C)(C)C
Reactant: CCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Product: C[C@@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)[C@@H](C)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1

Procedure:
This material is prepared from (R)-3-(1-oxopropyl)-4-(phenylmethyl)-2-oxazolidinone and 2-(S)-methyl-3-t-butyldimethylsiloxypropanal following the method of Evans and Gage, as described in Org. Syn., Vol. 68, 19xx, p. 83.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:13]#[N:14])[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([OH:12])[CH:6]=2.[F:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][C:21]=1[O:22][CH3:23]>>[F:15][C:16]1[CH:17]=[C:18]([C:2]2[CH:3]=[C:4]([C:13]#[N:14])[C:5]3[C:10]([CH:11]=2)=[CH:9][CH:8]=[C:7]([OH:12])[CH:6]=3)[CH:19]=[CH:20][C:21]=1[O:22][CH3:23]
Reactant: COc1ccc(B(O)O)cc1F
Reactant: N#Cc1cc(Br)cc2ccc(O)cc12
Product: COc1ccc(-c2cc(C#N)c3cc(O)ccc3c2)cc1F

Procedure:
The title compound was prepared by reacting 3-bromo-7-hydroxy-1-naphthonitrile (0.208 g, 0.839 mmol) with 3-fluoro-4-methoxyphenylboronic acid (0.18 g, 1.1 mmol) according to method A to yield 0.16 (65%) of a light yellow solid. An analytical sample was prepared by preparative reverse phase HPLC to yield the title compound as a white solid: mp 214-216° C.; 1H NMR (DMSO-d6): δ 3.90 (3H, s), 7.23-7.32 (2H, m), 7.37 (1H, d, J=2.24 Hz), 7.65-7.70 (1H, m), 7.79 (1H, dd, J=2.22 Hz, J=13.10 Hz), 8.03 (1H, d, J=8.96 Hz), 8.41 (1H, d, J=1.86 Hz), 8.50 (1H, d, J=1.43 Hz), 10.55 (1H, s); MS (ESI) m/z292 (M−H)−.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[C:8](=[O:14])[CH:7]=[CH:6]2.[CH2:15]([O:17][C:18]([C:20]1([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:19])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:15]([O:17][C:18]([C:20]1([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:2][C:3]3[CH:4]=[C:5]4[C:10](=[CH:11][CH:12]=3)[N:9]([CH3:13])[C:8](=[O:14])[CH:7]=[CH:6]4)[CH:27]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:19])[CH3:16]
Reactant: Cn1c(=O)ccc2cc(CBr)ccc21
Reactant: CCOC(=O)C1(c2cccc(O)c2)CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1(c2cccc(OCc3ccc4c(ccc(=O)n4C)c3)c2)CCOCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 60 %

Procedure:
A mixture of 6-bromomethyl-1-methyl-1,2-dihydroquinolin-2-one (0.1 g), 4-ethoxycarbonyl-4-(3-hydroxyphenyl)tetrahydropyran (0.098 g), potassium carbonate (0.057 g) and DMF (2 ml) was stirred at ambient temperature for 16 hours. The mixture was partitioned between diethyl ether and 0.5N aqueous hydrochloric acid. The organic layer was washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography using initially methylene chloride and then increasingly polar mixtures of methylene chloride and acetone as eluent. There was thus obtained an oil which was triturated in pentane to give 4-ethoxycarbonyl-4-[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-ylmethoxy)phenyl]tetrahydropyran (0.099 g, 60%), m.p. 109°-110° C.
Reaction SMILES: BrC1C=C([N:8]2[C:20]3[CH:19]=[C:18]4[C:21]([CH3:29])([CH3:28])[C:22]5[C:27]([C:17]4=[CH:16][C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][CH:13]=3)=[CH:26][CH:25]=[CH:24][CH:23]=5)C=C(Br)N=1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[CH3:28][C:21]1([CH3:29])[C:18]2=[CH:19][C:20]3[N:8]([C:34]4[CH:35]=[C:36]([C:33]5[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=5)[N:31]=[C:32]([C:33]5[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=5)[CH:33]=4)[C:9]4[C:14]([C:15]=3[CH:16]=[C:17]2[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[CH:13][CH:12]=[CH:11][CH:10]=4
Reactant: OB(O)c1cccnc1
Reactant: CC1(C)c2ccccc2-c2cc3c4ccccc4n(-c4cc(Br)nc(Br)c4)c3cc21
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: [Na+]
Solvent: COCCOC
Product: CC1(C)c2ccccc2-c2cc3c4ccccc4n(-c4cc(-c5cccnc5)nc(-c5cccnc5)c4)c3cc21

Procedure:
20 g (38.6 mmol) of 10-(2,6-dibromopyridin-4-yl)-12,12-dimethyl-10,12-dihydro-10-azaindeno[2,1-b]fluorene and 10.4 g of 3-pyridineboronic acid (84.9 mmol) are suspended in 400 ml of ethylene glycol dimethyl ether. 85 ml of a 2 M Na2CO3 solution are added to the reaction mixture. 2.23 g (1.93 mmol) of Pd(PPh3)4 are added to this suspension. The reaction mixture is heated under reflux for 12 h. After cooling, the precipitated solid is filtered off with suction, washed with water and ethanol and dried. The residue is extracted with hot toluene, recrystallised from toluene and finally sublimed in a high vacuum, the purity is 99.9%. Yield: 12 g, 60% of theory.