Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=1)[CH2:5][CH2:6][C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=1)(O)=[O:2].C(=O)(O)[O-].[Na+]>C1COCC1>[C:24]([C:21]1[CH:20]=[CH:19][C:18]([CH2:17][CH:4]([CH2:1][OH:2])[CH2:5][CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:15][CH:16]=2)=[CH:23][CH:22]=1)#[N:25]
Reactant: COC(=O)c1ccc(CCC(Cc2ccc(C#N)cc2)C(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(CCC(CO)Cc2ccc(C#N)cc2)cc1
Temperature: -5 °C
Reaction time: 4 h

Procedure:
47.43 ml (47.43 mmol) of a 1 M borane-THF complex solution are added dropwise to a solution of 8 g (23.71 mmol) of methyl 4-[3-carboxy-4-(4-cyanophenyl)butyl]benzoate from Example 47A in 200 ml of THF at −10° C. After the mixture has warmed to −5° C. it is stirred at this temperature for 4 h. After the reaction is complete, the reaction mixture is mixed with saturated sodium bicarbonate solution and the solvent is evaporated to dryness. The residue is taken up in dichloromethane, dried over sodium sulphate and, after filtration, again freed of solvent. The resulting crude product is purified by flash chromatography on silica gel (mobile phase: ethyl acetate/cyclohexane 1:10). 5.8 g (98% purity, 74% of theory) of a colourless solid are obtained.
Reaction SMILES: C(NC1C=C(OC)C=CC=1C1CCC2C=C(OC(=O)C(C)(C)C)C=CC=2C1)C.CN(C)C(C)(C)COC1C=CC(C=O)=CC=1.[CH3:45][N:46]([CH3:87])[C:47]([CH3:86])([CH3:85])[CH2:48][O:49][C:50]1[CH:84]=[CH:83][C:53]([CH2:54][CH2:55][CH2:56][NH:57][C:58]2[CH:63]=[C:62]([O:64][CH3:65])[CH:61]=[CH:60][C:59]=2[CH:66]2[CH2:75][CH2:74][C:73]3[CH:72]=[C:71]([O:76]C(=O)C(C)(C)C)[CH:70]=[CH:69][C:68]=3[CH2:67]2)=[CH:52][CH:51]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].N>O1CCCC1>[CH3:87][N:46]([CH3:45])[C:47]([CH3:85])([CH3:86])[CH2:48][O:49][C:50]1[CH:51]=[CH:52][C:53]([CH2:54][CH2:55][CH2:56][NH:57][C:58]2[CH:63]=[C:62]([O:64][CH3:65])[CH:61]=[CH:60][C:59]=2[CH:66]2[CH2:75][CH2:74][C:73]3[CH:72]=[C:71]([OH:76])[CH:70]=[CH:69][C:68]=3[CH2:67]2)=[CH:83][CH:84]=1
Reactant: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(NCCCc2ccc(OCC(C)(C)N(C)C)cc2)c1
Agent: CCNc1cc(OC)ccc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Agent: CN(C)C(C)(C)COc1ccc(C=O)cc1
Agent: N
Solvent: C1CCOC1
Product: COc1ccc(C2CCc3cc(O)ccc3C2)c(NCCCc2ccc(OCC(C)(C)N(C)C)cc2)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 72 %

Procedure:
Synthesized from pivalic acid 6-(2-ethylamino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester and 4-(2-dimethylamino-2-methylpropoxy)benzaldehyde according to an analogous synthetic method to Example 212, to a solution of the resulting pivalic acid 6-{2-{[4-(2-dimethylamino-2-methylpropoxy)benzyl]ethylamino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (73 mg) in tetrahydrofuran (1.5 ml) was added lithium aluminum hydride (20 mg), and the solution was stirred for 1.5 hours at room temperature. Tetrahydrofuran and aqueous ammonia were sequentially added thereto followed by stirring. The solution was then filtered through celite pad, the resulting residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system) to provide the title compound (45 mg).
Reaction SMILES: Cl[CH:2]=[CH:3][C:4]#[C:5][Si:6]([CH3:9])([CH3:8])[CH3:7].C(NCC)C.[C:15]1([O:21][C:22]([N:24]2[CH:37]([C:38]#[CH:39])[C:36]34[O:40][C:31]3([C:32](=[O:41])[CH2:33][CH2:34][CH2:35]4)[C:30]3[CH:29]=[CH:28][C:27]([O:42][C:43](=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45])=[CH:26][C:25]2=3)=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1C=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.[Cu]I>[C:15]1([O:21][C:22]([N:24]2[CH:37]([C:38]#[C:39]/[CH:2]=[CH:3]\[C:4]#[C:5][Si:6]([CH3:9])([CH3:8])[CH3:7])[C:36]34[O:40][C:31]3([C:32](=[O:41])[CH2:33][CH2:34][CH2:35]4)[C:30]3[CH:29]=[CH:28][C:27]([O:42][C:43](=[O:48])[C:44]([CH3:46])([CH3:45])[CH3:47])=[CH:26][C:25]2=3)=[O:23])[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C[Si](C)(C)C#CC=CCl
Reactant: C#CC1N(C(=O)Oc2ccccc2)c2cc(OC(=O)C(C)(C)C)ccc2C23OC12CCCC3=O
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Solvent: CCNCC
Product: CC(C)(C)C(=O)Oc1ccc2c(c1)N(C(=O)Oc1ccccc1)C(C#C/C=C\C#C[Si](C)(C)C)C13CCCC(=O)C21O3
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 32 %

Procedure:
A mixture of Pd(PPh3)4 (185 mg, 0.16 mmol), 1-chloro-4-(trimethylsilyl)-but-1-en-3-yne (0.776 g, 4.89 mmol), and diethylamine (0.51 mL, 4.93 mmol) in degassed benzene (5 mL) was stirred at 25° C. for 15 minutes. The resultant solution was added to a mixture of Compound 230 (1.50 g, 3.26 mmol) and CuI (124 mg, 0.65 mmol) in degassed benzene (15 mL) via a syringe followed by stirring at 25° C. for one hour. The reaction mixture was quenched by saturated aqueous NH4Cl, extracted with ethyl ether (80 mL), washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. Purification of the residue by flash column chromatography (silica gel, 25 percent ethyl ether in petroleum ether) provided a solid product Compound 231 (0.606 g, 32 percent): Rf =0.43 (silica, 50 percent ethyl ether in petroleum ether); IR (CHCl3) νmax 2964, 1721, 1494, 1378, 1305, 1270, 1253, 1202, 1181, 1122, 846 cm-1 ; 1H NMR (300 MHz, CDCl3) δ 8.40 (d, J=8.7 Hz, 1 H, H1), 7.44-7.10 (m, 6 H, H4 and aromatic), 6.99 (dd, J=8.7, 2.4 Hz, 1 H, H2), 5.98 (d, J=1.5 Hz, 1 H, H6), 5.84 (d, J=11.1 Hz, 1 H, olefinic), 5.69 (br d, J=11.1 Hz, 1 H, olefinic), 2.81-2.66 (m, 2 H, H9), 2.41-2.26 (m, 2 H, H7), 2.10-1.86 (m, 2 H, H8), 1.33 (s, 9 H, COC(CH3)3), 0.22 (s, 9 H, SiC(CH3)3); MS (FAB+) m/e (rel intensity) 582 (M+H, 100), 525 (13), 460 (48), 406 (8), 360 (6), 320 (8), 279 (25), 246 (5);HRMS for C34H36NO6Si (M+H), calcd 582.2312, found 582.2322.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]
Reactant: C1CCNC1
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(C=O)ccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(CN3CCCC3)ccc21
Yield: 103.8 %

Procedure:
In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (30.0 mg, 0.0730 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with pyrrolidine (0.096 mL, 1.2 mmol), acetic acid (0.084 mL, 1.5 mmol) and sodium triacetoxyborohydride (77 mg, 0.36 mmol). The reaction mixture was added with 1 mol/L hydrochloric acid and ethyl acetate, followed by extracting with 1 mol/L hydrochloric acid. The aqueous layer was added with sodium carbonate to adjust the pH to 9, then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-(pyrrolidin-1-ylmethyl)indol-2-yl]isoindolinone (35.3 mg).
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[S:15][C:16]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)=[CH:17][N:18]=3)[CH:5]=[CH:4][C:3]1=2.C([O:29][CH2:30][CH2:31][CH2:32][CH2:33]Br)(=O)C.[OH-].[Na+]>CO>[CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([C:14]3[S:15][C:16]([CH:19]4[CH2:24][CH2:23][N:22]([CH2:33][CH2:32][CH2:31][CH2:30][OH:29])[CH2:21][CH2:20]4)=[CH:17][N:18]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(-c3ncc(C4CCNCC4)s3)ccc21
Reactant: CC(=O)OCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)CCC(C)(C)c2cc(-c3ncc(C4CCN(CCCCO)CC4)s3)ccc21

Procedure:
The preparation was carried out as already described starting from 70 mg (0.20 mmol) of 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-5-yl]piperidine and 43 μl (0.30 mmol) of 4-bromobutyl acetate. The protecting group was cleaved off by means of a 1N NaOH solution in methanol. The product was purified by means of preparative HPLC and converted into the hydrochloride by treatment with methanolic HCl.
Reaction SMILES: C(Cl)(=O)CCCCCCCCCCCCCCCCCCCCC.[C:25]([OH:48])(=[O:47])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42]CCCC.C(Cl)(=O)C>C(Cl)(Cl)Cl>[C:25]([OH:48])(=[O:47])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCCCCCCC(=O)Cl
Solvent: CC(=O)Cl
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCC(=O)O
Reaction time: 0 h

Procedure:
Acylation was performed according to the invention on Whatman n0 2 paper with behenic acid chloride, behenic acid being a fatty acid with a saturated linear chain having C22. To this end, 500 mg of behenic acid were dissolved in 100 ml of chloroform in the presence of 500 mg of acetyl chloride. At the end of 15 minutes, a sample of paper was impregnated with the chloroform solution, the solvent was allowed to evaporate and a stream of gas at 150° C. was passed over the sample for 15 seconds. The presence of an excess of acetyl chloride made it possible, by means of a transchlorination reaction, to prepare behenic acid chloride extemporaneously. The excess of acetyl chloride was then eliminated by the gas stream by virtue of its high volatility. The very short dwell time of the acetyl chloride was, moreover, not sufficient for it to react significantly with the support. It was found that behenic acid was efficiently grafted onto the paper sample while providing a hydrophobic character very significantly greater than that provided by stearic acid.
Reaction SMILES: [CH3:1][N:2]([CH3:15])[C:3]([CH:5]1[S:10][C:9]2[S:11][CH:12]=[CH:13][C:8]=2[C:7](=O)[CH2:6]1)=O>O1CCCC1>[CH3:15][N:2]([CH2:3][CH:5]1[S:10][C:9]2[S:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6]1)[CH3:1]
Reactant: CN(C)C(=O)C1CC(=O)c2ccsc2S1
Solvent: C1CCOC1
Product: CN(C)CC1CCc2ccsc2S1
Reaction time: 3 h
Yield: 85.1 %

Procedure:
To a stirred, refluxing solution of N,N-dimethyl-4-oxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-6-carboxamide (7.57 g, 0.0314 mol) under nitrogen in tetrahydrofuran (150 ml) was added dropwise over 10 minutes borane-dimethylsulfide complex (9.4 ml, 0.094 mol). Stirring at reflux was continued for 3 hours and 6NHCl (25 ml) was added dropwise and reflux was continued for 1/2 hour. Most of the tetrahydrofuran was removed in vacuo and the residue was diluted with 6NHCl 50 ml) and was heated for 1/2 hour at steam bath temperature under nitrogen. The mixture was cooled in ice and water (100 ml) was added to dissolve the solid, washed with ether (50 ml) and basified with 10N NaOH (75 ml). The product was extracted into ethyl acetate (200 ml) in four portions, washed with water and dried over Na2SO4. The solution was filtered and concentrated in vacuo to obtain an amber oil (5.7 g). Yield was 85%.
Reaction SMILES: [CH3:1][C:2]([CH3:21])([CH3:20])[C:3]#[C:4][C:5]#[C:6][Sn](CCCC)(CCCC)CCCC.[O-:22][S:23]([C:26]([F:29])([F:28])[F:27])(=[O:25])=[O:24].C([I+:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)#N>>[O-:25][S:23]([C:26]([F:29])([F:28])[F:27])(=[O:24])=[O:22].[CH3:21][C:2]([CH3:1])([CH3:20])[C:3]#[C:4][C:5]#[C:6][I+:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: CCCC[Sn](C#CC#CC(C)(C)C)(CCCC)CCCC
Reactant: N#C[I+]c1ccccc1
Agent: O=S(=O)([O-])C(F)(F)F
Product: CC(C)(C)C#CC#C[I+]c1ccccc1
Yield: 84 %

Procedure:
(5,5-dimethyl-1,3-hexadiynyl)tri-n-butylstannane was reacted with cyano(phenyliodonium) triflate as described in the preceding paragraph, with the product workup according to procedure 1) producing an 84% yield of 5,5-dimethyl-1,3-hexadiynyl(phenyliodonium) triflate.
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[CH:20]=[C:19]([C@:24]3([CH3:30])[CH2:28][O:27][C:26](=[O:29])[NH:25]3)[CH:18]=[CH:17]4)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I:31]N1C(=O)CCC1=O.C(Cl)Cl>[Cl-].[Cl-].[Cl-].[Cl-].[Zr+4]>[C:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:15]([I:31])=[C:16]4[C:21](=[CH:22][CH:23]=3)[CH:20]=[C:19]([C@:24]3([CH3:30])[CH2:28][O:27][C:26](=[O:29])[NH:25]3)[CH:18]=[CH:17]4)[CH2:9][CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1CCC(=O)N1I
Reactant: C[C@@]1(c2ccc3cc(O[C@H]4CC[C@@H](c5ccccc5)CC4)ccc3c2)COC(=O)N1
Agent: [Zr+4]
Agent: [Cl-]
Solvent: ClCCl
Product: C[C@@]1(c2ccc3c(I)c(O[C@H]4CC[C@H](c5ccccc5)CC4)ccc3c2)COC(=O)N1

Procedure:
A mixture of (R)-4-(6-(cis-4-phenyl-cyclohexyloxy)naphthalen-2-yl)-4-methyloxazolidin-2-one (Example 30, 71.4 mg 0.000178 mol), N-iodosuccinimide (44.8 mg, 0.000199 mol) and zirconium tetrachloride (6.2 mg, 0.000027 mol) in methylene chloride (1.46 mL, 0.0228 mol) was heated to reflux under Ar in a vial for 6 h. LCMS showed the reaction to be completed. The precipitate was filtered off and the residue was purified with Isco column eluted with EtOAc in hexane from 0 to 40% to give (R)-4-(6-(trans-4-phenyl-cyclohexyloxy)-5-iodonaphthalen-2-yl)-4-methyloxazolidin-2-one as a solid (81.0 mg, 86% yield). LCMS 528.27 ([M+1], 80%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][C:3]=1[CH3:12].[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[F:13][C:14]1[CH:19]=[CH:18][C:17]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([CH3:12])[CH:4]=2)(=[O:10])=[O:9])=[CH:16][CH:15]=1
Reactant: Cc1cc(S(=O)(=O)Cl)ccc1Br
Reactant: Fc1ccccc1
Product: Cc1cc(S(=O)(=O)c2ccc(F)cc2)ccc1Br

Procedure:
The subtitle compound was prepared by the method of example 9 step (i) using 4-bromo-3-methylbenzene sulfonyl chloride and fluorobenzene.
Reaction SMILES: N[C@H](C(N1CCC[C@H]1C(N[C@H](C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(NCC([NH:73][C@H:74]([C:79](N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CCCCN)=O)CCCCN)=O)CCCCN)=O)CCCCN)=O)CCCCN)=O)CCCCN)=O)CCSC)=[O:80])[CH2:75][CH:76]([CH3:78])[CH3:77])=O)=O)CC1C=CC=CC=1)=O)CC1C=CC=CC=1)=O)CCC(=O)N)=O)CCC(=O)N)=O)=O)CCCCN)=O)=O)CCCNC(=N)N.P([O-])([O-])([O-])=[O:151]>>[NH2:73][C@H:74]([C:79]([OH:80])=[O:151])[CH2:75][CH:76]([CH3:77])[CH3:78]
Reactant: CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O
Reactant: O=P([O-])([O-])[O-]
Product: CC(C)C[C@H](N)C(=O)O
Reaction time: 0 h

Procedure:
The degradation of H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-(Lys)6-NH2 (SEQ ID NO: 111) (˜4.7×10−5 M) in 50 mM phosphate buffer solutions of pH 7.4 containing carboxypeptidase A (1 U/ml) was studied as described above. The pseudo first-order rate constant for the degradation was estimated to 5.5×10−3 min−1 and the corresponding half-life calculated to 126 min as previously described.
Reaction SMILES: C([O:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15][C:16]([C:18]1[N:19]=[C:20]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:37])[N:21]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[C:22]=1[Br:23])=[O:17])C1C=CC=CC=1.I[Si](C)(C)C>>[Br:23][C:22]1[N:21]([C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[C:20]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:37])=[N:19][C:18]=1[C:16]([NH:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]1[OH:8])=[O:17]
Reactant: O=C(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1nc(-c2ccccc2Cl)n(-c2ccc(Cl)cc2)c1Br
Agent: C[Si](C)(C)I
Product: O=C(N[C@H]1CCCC[C@@H]1O)c1nc(-c2ccccc2Cl)n(-c2ccc(Cl)cc2)c1Br

Procedure:
As described previously for Example 35, N-[(1S,2S)-2-(benzyloxy)cyclohexyl]-5-bromo-2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazole-4-carboxamide (Example 43) was de-benzylated by treatment with iodotrimethylsilane to give 5-bromo-2-(2-chlorophenyl)-1-(4-chlorophenyl)-N-[(1S,2S)-2-hydroxycyclohexyl]-1H-imidazole-4-carboxamide. LC-MS m/z 508.1 (MH+), retention time 2.96 min (method 2). 1H NMR (CD2Cl2, 400 MHz) δ 7.43 (d, 1H, Ph), 7.27 (m, 5H, Ph), 7.06 (m, 2H, Ph), 3.70 (m, 1H, CHOH), 3.44 (m, 1H, CHN), 1.95 (m, 2H, cyclohexane), 1.64 (m, 2H, cyclohexane), 1.24 (m, 4H, cyclohexane).
Reaction SMILES: [C:1]1([CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][OH:9]>C(Cl)(Cl)Cl.O>[O:9]1[CH:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:1][CH3:7])[CH2:8]1
Reactant: CO
Reactant: Cc1ccccc1
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCCCCCC1CO1

Procedure:
To a solution of 0.50 g of sixth generation PAMAM in 5 ml of methanol was added 0.56 g of epoxyoctane. After 6 days at room temperature, the solvent was evaporated in vacuo to give 0.80 g of colorless oil. The material was soluble in chloroform, toluene or methanol, but not soluble in water. The 13C-NMR spectrum was in accord with a dendrimer with C-8 alkyl groups attached to its terminal amines.
Reaction SMILES: C([O:5][C:6](=[O:29])[CH:7]=[CH:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[N:17]([CH2:18][CH2:19][CH:20]([OH:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C:16](=[O:27])[S:15][C:14]1=[O:28])(C)(C)C>FC(F)(F)C(O)=O>[OH:26][CH:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:19][CH2:18][N:17]1[C:16](=[O:27])[S:15][C:14](=[O:28])[N:13]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]=[CH:7][C:6]([OH:29])=[O:5]
Reactant: CCCCCC(O)CCn1c(=O)sc(=O)n1CCCCC=CC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CCCCCC(O)CCn1c(=O)sc(=O)n1CCCCC=CC(=O)O
Reaction time: 1 h
Yield: 101.4 %

Procedure:
A solution of 1.95 g (4.5 mmole) of 4-(3-hydroxyoctyl)-2,5-dioxo-1,3,4-thiadiazoline-3-heptanoic acid tert-butyl ester (6) in 10 ml of trifluoroacetic acid was kept at 0° for 1.5 hr and then evaporated at 0° under vacuum. Benzene (75 ml) was added to the residue and the solution re-evaporated. The remaining oil was stirred with 100 ml of 5% NaHCO3 for 1 hr and extracted with ether, the ether extract then being discarded. The remaining aqueous raffinate was then acidified with HCl and extracted with ether, giving 1.7 g of 4-(3-hydroxyoctyl)-2,5-dioxo-1,3,4-thiadiazoline-3-heptanoic acid (8); Rf =0.26 on silica gel, 1:1 CHCl3 --ether, I2 visualization. Acid 8 was identified by its solubility in 5% NaHCO3.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)=[O:8].O([CH2:26][C:27]([F:30])([F:29])[F:28])S(C(F)(F)F)(=O)=O>>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH:10]=1)=[O:8]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: O=C(Nc1nccs1)c1c[nH]c2ccccc12
Product: O=C(Nc1nccs1)c1cn(CC(F)(F)F)c2ccccc12

Procedure:
The title compound was prepared using 1H-indole-3-carboxylic acid thiazol-2-ylamide and 2,2,2-trifluoroethyl triflate as R5X.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:13][C:12](=[O:14])[C:11]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:23](OC(=O)C)(=[O:25])[CH3:24].N1C=CC=CC=1>CO>[Si:1]([O:8][CH:9]1[CH2:13][C:12](=[O:14])[C:11]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23](=[O:25])[CH3:24])=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)[Si](C)(C)OC1C=C(SCCCCCCO)C(=O)C1
Solvent: c1ccncc1
Solvent: CO
Product: CC(=O)OCCCCCCSC1=CC(O[Si](C)(C)C(C)(C)C)CC1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.5 %

Procedure:
700 mg (2.13 mmoles) of 4(RS)-t-butyldimethylsilyloxy-2-(6-hydroxyhexylthio)-2-cyclopentenone, 1020 mg (10 mmoles) of acetic anhydride and 1580 mg (20 mmoles) of pyridine were mixed, and stirred at room temperature for 2 hours. After the reaction, methanol was added. The solvent was removed to give 795 mg of 4-t-butyldimethylsilyloxy-2-(6-acetoxyhexylthio)-2-cyclopentenone as a nearly pure product.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:7]1)[CH3:2].Br[C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[C:24]([CH3:31])[C:23]=1[CH3:32]>>[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:10]([NH:11][C:22]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[C:24]([CH3:31])[C:23]=2[CH3:32])=[CH:9][C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:7]1)[CH3:2]
Reactant: CCOC(Cn1nc(-c2cccnc2)cc1N)OCC
Reactant: Cc1cc([N+](=O)[O-])cc(Br)c1C
Product: CCOC(Cn1nc(-c2cccnc2)cc1Nc1cc([N+](=O)[O-])cc(C)c1C)OCC

Procedure:
Analogously to Example 13A/Step 1, two batches of 100 mg (0.36 mmol) and of 1.50 g (5.43 mmol), respectively, of the compound of Example 4A and 92 mg (0.40 mmol) and 1.37 g (5.97 mmol), respectively, of 1-bromo-2,3-dimethyl-5-nitrobenzene gave a total of 1.31 g (23% of theory) of the title compound.
Reaction SMILES: [OH:1][CH:2]1[CH2:18][N:6]2[C:7](=[O:17])[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[N:10]=[C:5]2[NH:4][CH2:3]1.CS(O[CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[F:33])(=O)=O.[F-].[K+]>C(#N)C>[F:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[CH2:26][CH2:25][CH2:24][N:4]1[C:5]2=[N:10][C:9]([C:11]3[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=3)=[CH:8][C:7](=[O:17])[N:6]2[CH2:18][CH:2]([OH:1])[CH2:3]1
Reactant: CS(=O)(=O)OCCCc1ccccc1F
Reactant: O=c1cc(-c2ccncc2)nc2n1CC(O)CN2
Agent: [F-]
Agent: [K+]
Solvent: CC#N
Product: O=c1cc(-c2ccncc2)nc2n1CC(O)CN2CCCc1ccccc1F
Temperature: 80 °C

Procedure:
A suspension of 1.0 g (4.09 mmol) of 7-hydroxy-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one and 0.95 g (4.09 mmol) of 1-[3-(methylsulfonyloxy)propyl]-2-fluorobenzene in 100 ml of anhydrous acetonitrile was treated with 4.1 g (1.42 mmol) of potassium fluoride suspended on alumina (Fluka) and the resulting mixture was heated at 80° C. for 24 h.
Reaction SMILES: Br[CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([Br:12])=[CH:7][CH:8]=2)[C:3]1=O.[C:14]([NH2:22])(=[S:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[Br:12][C:6]1[CH:5]=[C:4]2[C:9]([CH2:10][CH2:11][C:2]3[S:21][C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)=[N:22][C:3]=32)=[CH:8][CH:7]=1
Reactant: NC(=S)c1ccccc1
Reactant: O=C1c2cc(Br)ccc2CCC1Br
Solvent: CCO
Product: Brc1ccc2c(c1)-c1nc(-c3ccccc3)sc1CC2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
0.3 g of 2,7-dibromo-3,4-dihydro-2H-naphthalen-1-one is dissolved in 10 ml of ethanol and, after addition of 140 mg of thiobenzamide, heated to reflux for 5 h. The reaction mixture is concentrated in vacuo, the residue is suspended in 10 ml of 1 N sodium hydroxide solution and stirred at room temperature for 1 h. The suspension is filtered with suction, thoroughly washed with water and dried in vacuo. 8-Bromo-2-phenyl4,5-dihydro-naphtho[1,2-d]thiazole is obtained with a melting point of 85° C.