Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5](I)=[CH:4][C:3]=1[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[Cl:18].[CH2:19]([Sn](CCCC)(CCCC)C=C)[CH2:20]CC>C1(C)C=CC=CC=1.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>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([CH:19]=[CH2:20])=[CH:4][C:3]=1[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[Cl:18]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: COc1cc(Cl)c(-c2cc(Cl)ccc2Cl)cc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: C=Cc1cc(-c2cc(Cl)ccc2Cl)c(Cl)cc1OC
Yield: 34.1 %

Procedure:
A mixture of 2,2′,5′-trichloro-5-iodo-4-methoxy-1,1′-biphenyl (1.17 g, 2.9 mmol), tributyl(vinyl)stannane (1.1 g, 3.5 mmol), Pd(PPh3)4 (670 mg, 0.6 mmol) in toluene (30 mL) was stirred at reflux under argon for 6 h. The reaction mixture was quenched with KF aqueous solution and then extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/DCM=100:1) to afford the desired product (310 mg, 35% yield) as a white solid.
Reaction SMILES: [CH3:1][Si:2]([C:5]1([Si](C)(C)C)[CH:9]=[CH:8][CH:7]=[CH:6]1)([CH3:4])[CH3:3].[B:14](Cl)([Cl:16])[Cl:15]>>[CH3:1][Si:2]([C:5]1([B:14]([Cl:16])[Cl:15])[CH:9]=[CH:8][CH:7]=[CH:6]1)([CH3:4])[CH3:3]
Reactant: ClB(Cl)Cl
Reactant: C[Si](C)(C)C1([Si](C)(C)C)C=CC=C1
Product: C[Si](C)(C)C1(B(Cl)Cl)C=CC=C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 84.7 %

Procedure:
16 g (0.076 mol) of the compound 1 were introduced into a round-bottomed flask equipped with a dry ice cooling bath. 8.9 g (0.076 mol) of BCl3 were condensed at -78° C. in a Schlenk tube and then added dropwise to the round-bottomed flask over a period of 5 minutes. The reaction mixture was warmed slowly to room temperature in the course of 1 hour and then kept at 55 to 60° C. for a further 2 hours. All the volatile compounds were removed in vacuo (3 mm Hg=4 mbar). Subsequent distillation at 39° C. under 0.012 mbar gave 14.1 g of the compound 2 (85% of the theoretical yield). The 1H-NMR agreed with the literature data and showed that a number of isomers had been prepared (cf. J. Organometallic Chem. 169 (1979), 327). 11B-NMR (64.2 MHz, C6D6): δ=+31.5.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]([OH:18])=O)[CH:14]=3)[NH:9][C:8]=2[C:19]2[C:20](=[O:31])[NH:21][N:22]=[C:23]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH:24]=2)[CH:4]=[N:3]1.C(N1CCOCC1)C.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.[CH:62]1([N:65]2[CH2:70][CH2:69][CH:68]([NH2:71])[CH2:67][CH2:66]2)[CH2:64][CH2:63]1>ClCCl>[CH:62]1([N:65]2[CH2:70][CH2:69][CH:68]([NH:71][C:16]([C:13]3[CH:14]=[C:15]4[C:10](=[CH:11][CH:12]=3)[NH:9][C:8]([C:19]3[C:20](=[O:31])[NH:21][N:22]=[C:23]([C:25]5[CH:26]=[CH:27][N:28]=[CH:29][CH:30]=5)[CH:24]=3)=[C:7]4[C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)=[O:18])[CH2:67][CH2:66]2)[CH2:64][CH2:63]1
Reactant: NC1CCN(C2CC2)CC1
Reactant: Cn1cc(-c2c(-c3cc(-c4ccncc4)n[nH]c3=O)[nH]c3ccc(C(=O)O)cc23)cn1
Agent: CCN1CCOCC1
Agent: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: Cn1cc(-c2c(-c3cc(-c4ccncc4)n[nH]c3=O)[nH]c3ccc(C(=O)NC4CCN(C5CC5)CC4)cc23)cn1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
100 mg of 3-(1-methyl-1H-pyrazol-4-yl)-2-(3-oxo-6-pyridin-4-yl-2,3-dihydro-pyridazin-4-yl)-1H-indole-5-carboxylic acid is dissolved in 3 ml of dichloromethane and 139 mg of N-ethylmorpholine and 43.6 mg of TOTU (O-((ethoxycarbonyl)-cyanomehyleneamino)-N,N, N′,N′-tetramethyluroniumtetrafluoro) is added. After 5 minutes 34 mg of 1-cyclopropyl-piperidin-4-ylamine is added. The reaction is stirred for 48 h at RT. The product is purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). Yield 47 mg. LC-MS (ES+) 535 (M+H)+.
Reaction SMILES: NC1NC2C=CC=CC=2N=1.[C:11](=O)(OC1C=CC=CC=1)[O:12]C1C=CC=CC=1.C1(O)C=CC=CC=1.C(NCCCC)CCC.[N:43]1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[NH:45][C:44]=1[NH:52][C:53]([NH:55][CH2:56][CH2:57][CH2:58][CH3:59])=[O:54].C(=O)([O-])[O-].[K+].[K+]>C(#N)C1C=CC=CC=1.N1C=CC=CC=1>[CH2:56]([N:55]1[C:11](=[O:12])[N:45]2[C:44](=[N:43][C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=32)[NH:52][C:53]1=[O:54])[CH2:57][CH2:58][CH3:59]
Reactant: CCCCNC(=O)Nc1nc2ccccc2[nH]1
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Agent: Nc1nc2ccccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: N#Cc1ccccc1
Solvent: c1ccncc1
Solvent: Oc1ccccc1
Product: CCCCn1c(=O)[nH]c2nc3ccccc3n2c1=O
Temperature: 160 °C
Reaction time: 15 h

Procedure:
A mixture of 100 g of 2-aminobenzimidazole and 188 g of diphenyl carbonate, 390 g of phenol and 0.1 g of pyridine was kept for 1 hour at 60°-68° C. and for 15 hours at 70° C. 63 g of dibutylamine were added and the reaction mixture was kept for 1 hour at 70° C. and for 3 hours at 100° C. For the reaction, according to the invention, of the resulting 1-(benzimidazol-2-yl)-3-(butyl)-urea, 241 g of diphenyl carbonate, 200 g of benzonitrile and 0.2 g of potassium carbonate, were added and the mixture was heated to 160° C. for 16 hours. The solvent was largely distilled off in vacuo and the residue was mixed with dibutyl ether. 3-Butyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole crystallized out as a crude product. This was separated off and washed with dibutyl ether. For purification, the crude product was boiled with 28 g of potassium hydroxide in 3 liters of water for 90 minutes. The hot solution was filtered. 3-Butyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole was isolated from the filtrate by acidification to a pH value of about 5. Melting point 275°-280° C.
Reaction SMILES: [OH:1][C@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@@H:4]([CH2:5][CH2:6][C:7]3[C:8]4[C@:19]([CH3:27])([CH2:20][CH2:21][C:22]=32)[C@@H:11]([C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:10][CH:9]=4)[C:3]1([CH3:29])[CH3:28].B(F)(F)F.CCO[CH2:37][CH3:38]>C1(O)CCCCC1>[CH:38]1([O:16][C:15](=[O:17])[CH2:14][CH2:13][C@H:12]([C@@H:11]2[C@:19]3([CH3:27])[C:8]([C:7]4[CH2:6][CH2:5][C@@H:4]5[C@:23]([C:22]=4[CH2:21][CH2:20]3)([CH3:26])[CH2:24][CH2:25][C@H:2]([OH:1])[C:3]5([CH3:28])[CH3:29])=[CH:9][CH2:10]2)[CH3:18])[CH2:37][CH2:4][CH2:3][CH2:2][CH2:25]1
Reactant: CCOCC
Reactant: C[C@H](CCC(=O)O)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3
Agent: FB(F)F
Solvent: OC1CCCCC1
Product: C[C@H](CCC(=O)OC1CCCCC1)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3
Temperature: 57.5 °C
Reaction time: 20 h

Procedure:
3β-Hydroxy-4,4-dimethyl-5α-chola-8,14-dien-24-oic acid (0.2 g) is suspended in 10 ml of cyclohexanol, 0.1 ml of boron trifluoride diethyl etherate is added and the mixture is stirred at 55-60° C. for 20 hours. After evaporation to dryness under reduced pressure, the remanens is purified by column chromatography and crystallized from methanol to give the title compound (49 mg). Melting point: 130-132° C. 1H-NMR (CDCl3): δ=5.35 (1H, s); 4.75 (1H, m); 3.24 (1H, m). MS: Calculated: 482.8. Found 482.4.
Reaction SMILES: [N:1]([CH2:4][C:5]1[O:9][N:8]=[C:7]([CH:10]([CH3:12])[CH3:11])[CH:6]=1)=[N+]=[N-].O1C2C=CC=CC=2C=C1CNC(=O)OC(C)(C)C>>[CH:10]([C:7]1[CH:6]=[C:5]([CH2:4][NH2:1])[O:9][N:8]=1)([CH3:12])[CH3:11]
Reactant: CC(C)c1cc(CN=[N+]=[N-])on1
Agent: CC(C)(C)OC(=O)NCc1cc2ccccc2o1
Product: CC(C)c1cc(CN)on1

Procedure:
(3-isopropylisoxazol-5-yl)methanamine was synthesized from 5-(azidomethyl)-3-isopropylisoxazole following the general procedure as described herein including the protection-deprotection steps to improve the purity of the amine.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH:3]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)[CH3:4].[C:13](=[O:16])([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:12][N:2]([CH3:1])[CH:3]([C:5]1[CH:6]=[C:7]([O:11][C:13](=[O:16])[N:2]([CH2:3][CH3:4])[CH3:1])[CH:8]=[CH:9][CH:10]=1)[CH3:4]
Reactant: CC(c1cccc(O)c1)N(C)C
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCN(C)C(=O)Oc1cccc(C(C)N(C)C)c1
Reaction time: 35 h

Procedure:
The process of the present invention for example involves reacting 3-[1-(dimethylamino)ethyl]phenol with N-ethyl-N-methyl-4-nitrophenyl carbamate in the presence of potassium carbonate and dimethyl sulfoxide at a temperature ranging from about 80° C. to about 120° C. for about 30 to 40 hours, to form racemate of ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester in the free base form. This racemate is then resolved to obtain the (S)-ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester. The preferred method of resolution of the (S)-isomer from the racemate involves dissolving a mixture of the free base of the racemate and (+)-di-O, O′-p-toluoyl tartaric acid monohydrate in a 2:1 mixture of methanol:water by heating, collecting the precipitate on cooling by filtration, crystallizing the precipitate from a 2:1 mixture of ethanol:water, and obtaining the substantially pure (S)-isomer by partitioning it between 1N sodium hydroxide and a suitable organic solvent. The base may further be converted to its pharmaceutically acceptable acid addition salts, such as L(+)-tartrate salt.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C=CC(O)=CC=1)O.[C:28](#[N:31])[CH:29]=[CH2:30]>>[C:28]([CH2:29][CH2:30][N:10]1[CH2:9][CH2:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[O:13][CH2:12][CH2:11]1)#[N:31]
Reactant: C=CC#N
Reactant: c1ccc(C2(c3ccccc3)CCNCCO2)cc1
Agent: Oc1ccc(O)cc1
Product: N#CCCN1CCOC(c2ccccc2)(c2ccccc2)CC1

Procedure:
The solution of 22.2 g of 7,7-diphenyl-hexahydro-1,4-oxazepine and 0.2 g of hydroquinone in 50 ml of acrylonitrile is refluxed for 18 hours, cooled and evaporated. The residue is taken up in chloroform, the mixture filtered through a short column of silica gel, eluted with chloroform and the eluate evaporated. The residue is recrystallized from ethanol, to yield the 4-(2-cyanoethyl)-7,7-diphenyl-hexahydro-1,4-oxazepine melting at 106°-107°.
Reaction SMILES: C(O)C.CS[C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][N:23]([C:26]4[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=4)[CH2:22][CH2:21]3)=[CH:13][CH:14]=2)[CH2:9]1)=[NH:7].[ClH:32].[CH3:33][NH2:34].C([O-])(=O)C.[Na+]>O>[ClH:32].[ClH:32].[CH3:33][NH:34][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]3[CH2:21][CH2:22][N:23]([C:26]4[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=4)[CH2:24][CH2:25]3)=[CH:13][CH:14]=2)[CH2:9]1)=[NH:7]
Reactant: CN
Reactant: CSC(=N)N1CCc2ccc(OCC3CCN(c4ccncc4)CC3)cc2C1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CNC(=N)N1CCc2ccc(OCC3CCN(c4ccncc4)CC3)cc2C1
Temperature: 80 °C
Reaction time: 3 h
Yield: 119.4 %

Procedure:
To an ethanol solution (2 ml) of 7-[1-(pyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carbothioimidic acid methyl ester (100 mg) were added methylamine hydrochloride (20 mg) and sodium acetate (25 mg), and the mixture was stirred at 80° C. for 3 hours. After completion of the reaction, water was added and the mixture was washed with chloroform. Thereto was added aqueous sodium hydrogencarbonate solution and the mixture was washed with chloroform. To the aqueous layer was added 4N aqueous sodium hydroxide solution and the mixture was extracted with chloroform. The extract was washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated and the obtained residue was treated with hydrogen chloride—ethanol solution and dried under reduced pressure to give the title compound (80 mg).
Reaction SMILES: [C:1]([C:6](=[CH:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][OH:21])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:5])[CH2:2][CH2:3][CH3:4].[C:22](Cl)(=[O:31])[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1>N1C=CC=CC=1>[C:1]([C:6](=[CH:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][O:21][C:22](=[O:31])[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: CCCC(=O)C(=CNc1ccccc1CO)C(=O)OCC
Solvent: c1ccncc1
Product: CCCC(=O)C(=CNc1ccccc1COC(=O)c1ccc(OC)cc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 16 h
Yield: 57.8 %

Procedure:
Ethyl 2-butyryl-3-(2-(hydroxymethyl)phenylamino)-acrylate (14.6 g, 50 mmol) was dissolved in pyridine (50 ml), cooled in ice, and p-anisoyl chloride (12.8 g, 75 mmol), added dropwise. The mixture was stirred 16 hours with warming to room temperature, then evaporated, taken up in dichloromethane, washed with aqueous sodium bicarbonate, dried and evaporated. Crystallization from ether gave ethyl 2-butyryl-3-(2-(4-methoxybenzoyloxymethyl)phenylamino)acrylate (12.3 g, 58%).
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[N+:6]([C:9]1[C:14]([CH2:15][OH:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=1)([O-:8])=[O:7].CCN(CC)CC.C(Cl)Cl>CN(C1C=CN=CC=1)C.C(Cl)(Cl)Cl>[Br:1][CH2:2][C:3]([O:16][CH2:15][C:14]1[CH:13]=[C:12]([O:17][CH3:18])[C:11]([O:19][CH3:20])=[CH:10][C:9]=1[N+:6]([O-:8])=[O:7])=[O:4]
Reactant: COc1cc(CO)c([N+](=O)[O-])cc1OC
Reactant: O=C(Br)CBr
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: COc1cc(COC(=O)CBr)c([N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 5 h
Yield: 55.1 %

Procedure:
Bromoacetylbromide (0.19 ml, 2.2 mmol) was slowly added to the solution of 6-nitroveratrylalcohol (0.43 g, 2 mmol), Et3N (0.56 ml, 4 mmol) and DMAP (24 mg, 0.2 mmol) in CHCl3 (5 ml). After stirring at room temperature for five hours, CH2Cl2 (20 ml) was added and the mixture was washed with HCl (1 M, 2×10 ml), NaHCO3 (sat., 10 ml) and water (10 ml). Organic phase was dried over Na2SO4, evaporated and purified by chromatography (Si-gel, CH2Cl2) to yield 4.5-dimethoxy-2-nitrobenzyl 2-bromoacetate (368 mg, 55%).
Reaction SMILES: C(N(CC)C(C)C)(C)C.C(Cl)(=O)OCC(C)C.[C:18]([O:22][C:23]([NH:25][C@H:26]([CH3:30])[C:27]([OH:29])=O)=[O:24])([CH3:21])([CH3:20])[CH3:19].[Si]([CH:35]=[N+:36]=[N-:37])(C)(C)C>O1CCCC1.C(#N)C>[N+:36](=[CH:35][C:27](=[O:29])[C@H:26]([NH:25][C:23](=[O:24])[O:22][C:18]([CH3:19])([CH3:20])[CH3:21])[CH3:30])=[N-:37]
Reactant: C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: C[Si](C)(C)C=[N+]=[N-]
Agent: CC(C)COC(=O)Cl
Solvent: CC#N
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H](NC(=O)OC(C)(C)C)C(=O)C=[N+]=[N-]
Temperature: 0 °C
Reaction time: 4 h

Procedure:
N,N-Diisopropylethylamine (4.7 mL, 27 mmol) and isobutyl carbonochloridate (3.11 ml, 23.78 mmol) were added to a solution of (R)-2-((tert-butoxycarbonyl)amino)propanoic acid (3.0 g, 15.9 mmol) in tetrahydrofuran (34.5 ml) at 0° C. and the mixture was stirred at 0° C. for four hours. The mixture was then diluted with acetonitrile (22 mL). TMS-diazomethane (2.0 M in diethyl ether, 15.9 ml, 31.7 mmol) was then added slowly to the mixture at 0° C. The mixture was allowed to stir at 0° C. for 3 hours and was then allowed to warm to room temperature for 14 hours. The mixture was concentrated under reduced pressure and then purified by column chromatography on silica to afford (R)-tert-butyl (4-diazo-3-oxobutan-2-yl)carbamate. 1H NMR (500 MHz, DMSO-d6) δ 7.27 (d, J=7.4 Hz, 1H), 6.01 (s, 1H), 3.97-3.87 (m, 1H), 1.37 (s, 9H), 1.13 (d, J=7.3 Hz, 3H).
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[O:16][CH:17]=[CH:18][CH:19]=2)[CH2:13][NH:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[C:26]([O:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1)=[O:27]>O1CCCC1.O>[Si:1]([O:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[O:16][CH:17]=[CH:18][CH:19]=2)[CH2:13][N:12]([C:26]([O:28][C:29]2[CH:30]=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][CH:38]=2)=[O:27])[CH2:11]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CNC[C@@H]1c1ccco1
Reactant: COC(=O)c1ccc(OC(=O)Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OC(=O)N2C[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](c3ccco3)C2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 350 mg portion of (3R,4R)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2-furyl)pyrrolidine and 470 mg of sodium bicarbonate were suspended in 20 ml of a tetrahydrofuran-water (3:1) mixed solvent, and 320 mg of methyl 4-[(chlorocarbonyl)oxy]benzoate (mfd. by Fluka) was added in one portion thereto at room temperature. After 1Hour of stirring at room temperature, 80 mg of methyl 4-[(chlorocarbonyl)oxy]benzoate was further added thereto at room temperature. After 2 hours of further stirring, the reaction solution was concentrated under a reduced pressure. The residue was separated by diluting it with water and diethyl ether, and then extracted with diethyl ether. The organic layer was washed with water and saturated brine in that order and dried with anhydrous sodium sulfate. This was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-ethyl acetate) to obtain 571 mg of 4-(methoxycarbonyl)phenyl (3R,4R)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2-furyl)pyrrolidine-1-carboxylate as a colorless oily substance.
Reaction SMILES: [CH3:1][C:2]([N:4]([OH:39])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([CH2:13][CH2:14][C:15]([N:17]([OH:38])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([CH2:26][CH2:27][C:28]([N:30]([OH:37])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][NH2:36])=[O:29])=[O:25])=[O:16])=[O:12])=[O:3].[CH:40]1[C:45](N=C=S)=[CH:44][C:43]2[C:49]([O:51][C:52]3([C:62]4[CH:63]=[CH:64][C:65]([OH:67])=[CH:66][C:61]=4[O:60][C:54]4[CH:55]=[C:56]([OH:59])[CH:57]=[CH:58][C:53]3=4)[C:42]=2[CH:41]=1)=[O:50]>[Al]>[CH:40]1[CH:45]=[CH:44][C:43]([C:49]([OH:51])=[O:50])=[C:42]([C:52]2[C:53]3[CH:58]=[CH:57][C:56]([OH:59])=[CH:55][C:54]=3[O:60][C:61]3[C:62]=2[CH:63]=[CH:64][C:65]([CH:66]=3)=[O:67])[CH:41]=1.[CH3:1][C:2]([N:4]([OH:39])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([CH2:13][CH2:14][C:15]([N:17]([OH:38])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([CH2:26][CH2:27][C:28]([N:30]([OH:37])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][NH2:36])=[O:29])=[O:25])=[O:16])=[O:12])=[O:3]
Reactant: O=C1OC2(c3ccc(O)cc3Oc3cc(O)ccc32)c2ccc(N=C=S)cc21
Agent: CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN
Agent: [Al]
Product: O=C(O)c1ccccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12

Procedure:
An aliquot of 120 mg of Desferrioxamine and 233.64 mg of fluorescein isothiocyanate (FITC) are mixed in 50 ml of 0.1 M Na carvonate pH 9.5. A molar ratio of 3:1 of FITC: Desferrioxamine is used as described in Hentz et al. (1997) Anal. Chem. 69:4994-5000. The reaction mixture is wrapped in aluminum foil to avoid light exposure and allowed to react for at least 24 hours at room temperature. To separate fluorescent-Desferrioxamine from free fluorescein and free Desferrioxamine, the mixture is electrophoresed over a P-2 column (Bio-Rad) equilibrated in saline and samples are eluted in 2 ml fractions. The fluorescein-Desferrioxamine is eluted in the void volume of the column. The first peak is collected and used for preparing fluorescein-Desferrioxamine, Desferrioxamine, and rhodamine-liposomes.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[N:5]=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.ClCCl.C([O-])(=O)C.[K+].Br[C:45]1[S:46][C:47]2[C:53]([C:54]3[CH:59]=[CH:58][C:57]([Cl:60])=[CH:56][CH:55]=3)=[C:52]([C@H:61]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[C:62]([O:64][CH2:65][CH3:66])=[O:63])[C:51]([CH3:72])=[CH:50][C:48]=2[N:49]=1.C([O-])([O-])=O.[K+].[K+]>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:68]([O:67][C@@H:61]([C:52]1[C:51]([CH3:72])=[CH:50][C:48]2[N:49]=[C:45]([C:2]3[CH:3]=[C:4]([C:8]4[CH:9]=[C:10]5[C:14](=[CH:15][CH:16]=4)[N:13]([CH3:17])[N:12]=[CH:11]5)[N:5]=[N:6][CH:7]=3)[S:46][C:47]=2[C:53]=1[C:54]1[CH:55]=[CH:56][C:57]([Cl:60])=[CH:58][CH:59]=1)[C:62]([O:64][CH2:65][CH3:66])=[O:63])([CH3:69])([CH3:70])[CH3:71]
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(Br)sc2c1-c1ccc(Cl)cc1
Reactant: Cn1ncc2cc(-c3cc(Cl)cnn3)ccc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(=O)[O-]
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Solvent: ClCCl
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3cnnc(-c4ccc5c(cnn5C)c4)c3)sc2c1-c1ccc(Cl)cc1
Temperature: 110 °C

Procedure:
5-(5-chloropyridazin-3-yl)-1-methyl-1H-indazole (75.0 mg, 0.307 mmol), bis(pinacolato)diboron (101.2 mg, 0.398 mmol), [1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (37.5 mg, 0.046 mmol), and potassium acetate (90.2 mg, 0.920 mmol) were taken in a microwave vial, and the vial was vacuum pumped and flushed with argon three times. To this mixture was added degassed DMF (3 mL). The reaction mixture was heated at 110° C. for 2 h then cooled. To the cooled reaction mixture was added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (180.0 mg, 0.368 mmol), tetrakis(triphenylphosphine)palladium(0) (53.1 mg, 0.046 mmol), K2CO3 (127.1 mg, 0.920 mmol) and degassed water (0.5 mL). The reaction mixture was heated to 110° C. for 2 h, cooled, filtered through Celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. LCMS-ESI+ calc'd for C34H33ClN5O3S (M+H+): 626.2; Found: 625.5 (M+H+).
Reaction SMILES: [C:1]([CH:5]1[CH2:17][CH2:16][C:8]2([O:12][N:11]=[C:10]([C:13]([OH:15])=O)[CH2:9]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[C:21]([F:30])[CH:20]=1>C1COCC1>[F:30][C:21]1[CH:20]=[C:19]([NH:18][C:13]([C:10]2[CH2:9][C:8]3([CH2:7][CH2:6][CH:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:17][CH2:16]3)[O:12][N:11]=2)=[O:15])[CH:24]=[CH:23][C:22]=1[NH:25][S:26]([CH3:29])(=[O:28])=[O:27]
Reactant: CC(C)(C)C1CCC2(CC1)CC(C(=O)O)=NO2
Reactant: CS(=O)(=O)Nc1ccc(N)cc1F
Solvent: C1CCOC1
Product: CC(C)(C)C1CCC2(CC1)CC(C(=O)Nc1ccc(NS(C)(=O)=O)c(F)c1)=NO2
Reaction time: 72 h

Procedure:
The acid 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid (359 mg, 1.5 mmol) was dissolved in THF (15 ml). N,N′-carbonyldiimidazole (243.5 mg, 1.5 mmol) was added while stirring. For activation, the mixture was stirred for 1 h at RT. The N-(4-amino-2-fluorophenyl)methanesulphonamide (326.8 mg, 1.60 mmol) was then added as a solid. The course of the reaction was controlled by DC. After 3 d only small amounts of starting products could still be seen in the DC. For working up, THF was removed by distillation. The residue was dissolved in 0.5 N aq. HCl (10 ml) and EtOAc (40 ml). The phases were separated. The organic phase was washed successively with 0.5 N aq. HCl (2×8 ml), with water (1×10 ml), with 1.1 M aq. NaHCO3 solution (3×7 ml) and water (3×10 ml). The organic phase was dried with Na2SO4. The solvent was removed by distillation. The light brown residue was stirred out with diethyl ether (3×2 ml). The solvent was in each case removed by suction-filtration. The light pink residue was the mixture of the diastereoisomers of 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(3-fluoro-4-methanesulphonylaminophenyl)amide (353 mg, mp 104-107° C. and 228-232° C., 55%).