Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C@H]1C2C(=CC(Br)=CC=2)[C@@H](NC[C@@H](O)[C@@H](N)CC2C=C(F)C=C(F)C=2)C1)C=C.[CH3:30][N:31]([C@@H:39]([CH2:43][CH2:44][CH:45]=[CH2:46])[C:40]([OH:42])=O)[C:32](=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].[CH2:47]([O:50][CH:51]1[C:59]2[C:54](=[CH:55][C:56]([O:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[CH:57][CH:58]=2)[CH:53]([NH:67][CH2:68][C@@H:69]([O:79][Si:80]([C:83]([CH3:86])([CH3:85])[CH3:84])([CH3:82])[CH3:81])[C@@H:70]([NH2:78])[CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[CH2:52]1)[CH:48]=[CH2:49]>>[CH2:47]([O:50][CH:51]1[C:59]2[C:54](=[CH:55][C:56]([O:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[CH:57][CH:58]=2)[CH:53]([NH:67][CH2:68][C@@H:69]([O:79][Si:80]([C:83]([CH3:86])([CH3:85])[CH3:84])([CH3:81])[CH3:82])[C@@H:70]([NH:78][C:40](=[O:42])[C@@H:39]([N:31]([CH3:30])[C:32](=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:43][CH2:44][CH:45]=[CH2:46])[CH2:71][C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[CH2:52]1)[CH:48]=[CH2:49]
Reactant: C=CCC[C@@H](C(=O)O)N(C)C(=O)CCCCC
Reactant: C=CCOC1CC(NC[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](N)Cc2ccccc2)c2cc(Oc3ccccc3)ccc21
Agent: C=CCO[C@@H]1C[C@H](NC[C@@H](O)[C@@H](N)Cc2cc(F)cc(F)c2)c2cc(Br)ccc21
Product: C=CCC[C@@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](CNC1CC(OCC=C)c2ccc(Oc3ccccc3)cc21)O[Si](C)(C)C(C)(C)C)N(C)C(=O)CCCCC
Yield: 39.6 %

Procedure:
Step EX (1): (S)-2-(N-methylhexanamido)hex-5-enoic acid (500 mg, 2.1 mmol) and (2R,3S)-N1-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-4-phenylbutane-1,3-diamine (1.2 g, 2.1 mmol, from Preparation BC) were coupled using a procedure analogous to Step CA (1) to afford 650 mg (40% yield) of (2S)-N-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-yl)-2-(N-methylhexanamido)hex-5-enamide. LC-MS (M+H)+=782.65; 1H NMR (300 MHz, CDCl3) δ ppm 0.0 (m, 6H) 0.6-0.9 (m, 12H) 1.1-1.4 (m, 6H) 1.4-1.6 (m, 3H) 1.7-2.3 (m, 6H) 2.3-2.4 (s, 3H) 2.5-2.9 (m, 4H) 3.5-3.8 (m, 1H) 4.0-4.4 (m, 4H) 4.7-4.8 (m, 1H) 4.8-5.4 (m, 4H) 5.6-6.1 (m, 2H) 6.9-7.4 (m, 13H).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([C:13]1[CH:30]=[CH:29][C:16]([O:17][CH2:18][CH2:19][N:20]([CH2:26][CH2:27][OH:28])[C:21]([N:23]([CH3:25])[CH3:24])=[O:22])=[CH:15][CH:14]=1)#[N:12].C(N(CC)CC)C>ClCCl>[C:11]([C:13]1[CH:14]=[CH:15][C:16]([O:17][CH2:18][CH2:19][N:20]([CH2:26][CH:27]=[O:28])[C:21]([N:23]([CH3:24])[CH3:25])=[O:22])=[CH:29][CH:30]=1)#[N:12]
Reactant: CN(C)C(=O)N(CCO)CCOc1ccc(C#N)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CN(C)C(=O)N(CC=O)CCOc1ccc(C#N)cc1
Temperature: -30 °C
Reaction time: 3 h
Yield: 50.3 %

Procedure:
Oxalyl chloride (6.3 g, 0.0497 mol) was added dropwise to a stirred solution of DMSO (7.6 g, 0.094 mol) and dichloromethane (100 mL) at −78° C. After stirring for 15 min at the same temperature, 1-[2-(4-cyanophenoxy)ethyl]-1-(2-hydroxyethyl)-3,3-dimethylurea (6 g, 0.0325 mol; see step (i) above) in dichloromethane was added and stirring continued for 3 h under a nitrogen atmosphere. Triethylamine (16.4 mL, 0.1625 mol) was added dropwise and the reaction mixture was then warmed slowly to −30° C. The reaction mixture was quenched with an aqueous solution of citric acid, and the resulting mixture extracted with dichloromethane. The organic layer was washed with water and brine and dried over sodium sulfate. Solvent evaporation under reduced pressure yielded 4.5 g of the crude title compound, which was used without further purification.
Reaction SMILES: [C:1]([O:4][C@H:5]([CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[N:22]=[C:23]([C:27]3[O:28][CH:29]=[CH:30][CH:31]=3)[O:24][C:25]=2[CH3:26])=[C:15]([O:32][CH3:33])[CH:14]=1)[C:6](OC)=[O:7])(=[O:3])[NH2:2].C1CCN2C(=NCCC2)CC1>C(Cl)(Cl)Cl>[O:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[C:23]1[O:24][C:25]([CH3:26])=[C:21]([CH2:20][O:19][C:16]2[CH:17]=[CH:18][C:13]([CH2:12][CH2:11][CH2:10][C@H:5]3[O:4][C:1](=[O:3])[NH:2][C:6]3=[O:7])=[CH:14][C:15]=2[O:32][CH3:33])[N:22]=1
Reactant: COC(=O)[C@@H](CCCc1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1)OC(N)=O
Solvent: ClC(Cl)Cl
Solvent: C1CCC2=NCCCN2CC1
Product: COc1cc(CCC[C@H]2OC(=O)NC2=O)ccc1OCc1nc(-c2ccco2)oc1C
Reaction time: 1 h
Yield: 90.6 %

Procedure:
To a solution of methyl (R)-(+)-2-carbamoyloxy-5-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxyphenyl]pentanoate (2.92 g) in chloroform (100 ml) was added dropwise, at temperature ranging from -5 to 0° C., 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) (1.54 g). The mixture was stirred for one hour at the same temperature range. The reaction mixture was washed with 2N HCl and water, which was then dried (MgSO4) and concentrated to yield (R)-(+)-5-[3-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxyphenyl]propyl]-2,4-oxazolidinedione (2.46 g, 91%), which was recrystallized from acetone-isopropyl ether to give colorless needles, m.p.122-123° C. [α]D +39.4° (c=0. 495, CHCl3)
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[N:29]1([C:33]2[NH:37][C:36]3[CH:38]=[CH:39][CH:40]=[CH:41][C:35]=3[N:34]=2)[CH2:32][CH2:31][CH2:30]1>>[N:29]1([C:33]2[N:34]([C:2]3[N:10]=[C:9]4[C:5]([N:6]=[C:7]([CH2:12][N:13]5[CH2:14][CH2:15][CH:16]([C:19]([OH:22])([CH3:20])[CH3:21])[CH2:17][CH2:18]5)[N:8]4[CH3:11])=[C:4]([N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[N:3]=3)[C:35]3[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=3[N:37]=2)[CH2:32][CH2:31][CH2:30]1
Reactant: Cn1c(CN2CCC(C(C)(C)O)CC2)nc2c(N3CCOCC3)nc(Cl)nc21
Reactant: c1ccc2[nH]c(N3CCC3)nc2c1
Product: Cn1c(CN2CCC(C(C)(C)O)CC2)nc2c(N3CCOCC3)nc(-n3c(N4CCC4)nc4ccccc43)nc21

Procedure:
2-(1-((2-Chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (75 mg) was reacted with 2-(azetidin-1-yl)-1H-benzo[d]imidazole (33 mg) via General Procedure I for Buchwald coupling to give 35.9 mg 455 following reverse phase purification. MS (Q1) 546.3 (M)+
Reaction SMILES: [CH:1]1([NH:7][C:8](=[O:39])[N:9]([CH2:18][CH2:19][O:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([CH2:27][CH2:28][CH:29]([CH2:37][CH3:38])[C:30]([O:32]C(C)(C)C)=[O:31])[CH2:22]2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C1(C)C=CC=CC=1>ClCCl>[CH:1]1([NH:7][C:8](=[O:39])[N:9]([CH2:18][CH2:19][O:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([CH2:27][CH2:28][CH:29]([CH2:37][CH3:38])[C:30]([OH:32])=[O:31])[CH2:22]2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCC(CC[C@H]1CCC[C@@H](OCCN(Cc2ccc(C)cc2)C(=O)NC2CCCCC2)C1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCC(CC[C@H]1CCC[C@@H](OCCN(Cc2ccc(C)cc2)C(=O)NC2CCCCC2)C1)C(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 85.7 %

Procedure:
160 mg of tert-butyl 4-(cis-3-{2-[3-cyclohexyl-1-(4-methylbenzyl)ureido]ethoxy}cyclohexyl)-2-ethylbutyrate are dissolved in 16 ml of dichloromethane, and 4 ml of trifluoroacetic acid are added. The mixture is stirred at room temperature for 12 hours. 50 ml of toluene are then added, and the solvents are removed under reduced pressure. The residue is purified by RP-HPLC. Freeze drying gives 123 mg of 4-(cis-3-{2-[3-cyclohexyl-1-(4-methylbenzyl)ureido]ethoxy}cyclohexyl)-2-ethylbutyric acid as a colorless oil. C29H46N2O4 (486.70), MS(ESI): 487 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]=[CH:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:22](Cl)(=[O:25])[CH2:23][CH3:24]>ClCCl.CN(C)C(N)CC>[C:22]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:13][CH:14]=1)(=[O:25])[CH2:23][CH3:24]
Reactant: CCOC(=O)C=Cc1ccc(N)cc1
Reactant: CCC(=O)Cl
Agent: CCC(N)N(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)C=Cc1ccc(NC(=O)CC)cc1
Reaction time: 1 h
Yield: 87.9 %

Procedure:
To a mixture of ethyl 4-aminocinnamate (300 mg), triethylamine (167 mg) and dichloromethane (3 ml) was added a solution of propionyl chloride (182 mg) in dichloromethane (1 ml) in an ice-water bath, and the mixture was stirred for 1 hour at the same temperature. To the reaction mixture was added 4 drops of N,N-dimethylpropanediamine, and the mixture was further stirred for 5 minutes. The reaction mixture was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The residue was crystallized from diisopropyl ether to give ethyl 4-propionamidocinnamate (341 mg) as a colorless powder.
Reaction SMILES: C([NH:5][C:6](=[O:69])[C@H:7]([CH:66]([CH3:68])[CH3:67])[CH2:8][C@H:9](O)[C@@H:10](NC(=O)C(C1N2C=C(C3C=NC=CC=3)N=C(CCC)C2=NN=1)CC1N=CN(C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=1)[CH2:11]C1CCCCC1)CCC>FC(F)(F)C(O)=O.O>[CH:66]([CH:7]([CH2:8][CH2:9][CH2:10][CH3:11])[C:6]([NH2:5])=[O:69])([CH3:68])[CH3:67]
Reactant: CCCCNC(=O)[C@@H](C[C@H](O)[C@H](CC1CCCCC1)NC(=O)C(Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)c1nnc2c(CCC)nc(-c3cccnc3)cn12)C(C)C
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CCCCC(C(N)=O)C(C)C
Yield: 189.4 %

Procedure:
A solution of (2S,4S,5S)-N-butyl-6-cyclohexyl-4-hydroxy-2-isopropyl-5-[3-(1-triphenylmethylimidazol-4-yl)-(2RS)-2-(8-propyl-6-(3-pyridyl)-1,2,4-triazolo[4,3-a]pyrazin-3-yl)propionamido]hexanamide (A) (187 mg) in trifluoroacetic acid (8 ml) and water (2 ml) was stirred for 75 minutes. Volatile material was removed by evaporation and saturated sodium hydrogen carbonate solution (10 ml) added to the residue. The mixture was extracted with chloroform (2×20 ml) and the combined extracts were washed successively with water (10 ml) and saturated sodium chloride solution (10 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue triturated with ether to give (2S,4S,5S)-N-butyl-6-cyclohexyl-4-hydroxy-5-[3-a]pyrazin-3-yl)propionamido]-2-isopropylhexanamide as a white powder (60 mg); NMR (d6 -DMSO/d4 -acetic acid): 0.3-1.7 (complex m, 32H), 2.0 (m, 3H), 2.9-3.9 (complex m, 8H), 4.9 (m, 1H), 7.3 (m, 1H), 7.6 (m, 1H), 8.5 (m, 2H), 8.7 (m, 1H), 9.25 and 9.35 (both S, ratio 1:1, total 1H), 9.3 (m, 1H); mass spectrum (+ve FAB, DMSO): 686 (M+H)+, 360, 332.
Reaction SMILES: Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:11][O:12][C:13](=[O:43])[C@H:14]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Sn](CCCC)(CCCC)CCCC)=[CH:26][CH:25]=1)[NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]>CN(C=O)C.ClCCl.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>[CH3:11][O:12][C:13](=[O:43])[C@H:14]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:2]2[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Cl:8])[CH:7]=2)=[CH:28][CH:29]=1)[NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17]
Reactant: Cn1cc(Cl)cc(Br)c1=O
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)OC)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COC(=O)[C@H](Cc1ccc(-c2cc(Cl)cn(C)c2=O)cc1)NC(=O)OC(C)(C)C
Temperature: 90 °C
Reaction time: 4 h
Yield: 53.6 %

Procedure:
A solution of 3-bromo-5-chloro-1-methyl-2-pyridone (660 mg, 2.97 mmol) and N-[(1,1-dimethylethoxy)carbonyl]-4-[(tributyl)stannyl]-L-phenylalanine methyl ester (1.7 g, 2.99 mmol) in DMF (30 mL) was deoxygenated by alternately freezing the mixture in a liquid nitrogen bath under vacuum and thawing under argon (3×). Tetrakis(triphenylphosphine)palladium (140 mg, 0.20 mmol) was added and the mixture was heated to 90° C. for 3 hr as the mixture turned dark. TLC indicated that the reaction was not complete and an additional 140 mg portion of the catalyst was added and heating continued for 4 hr. The mixture was allowed to cool and was diluted with dichloromethane and was filtered through a pad of celite. The filtrate was evaporated to dryness and the residue was dissolved in 1:1 ether:ethyl acetate (60 mL). The solution was washed with water (3×10 mL) and brine (1×10 mL) and was dried (MgSO4). The residue obtained upon concentration was chromatographed over 150 g of silica gel eluting with 7:3 ethyl acetate:hexane to give 4-(5-chloro-1-methyl-2-oxo-3-pyridinyl)-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl ester (670 mg, 54%). LRMS-Electrospray: m/z 863 (2M+Na), 858 (2M+NH4), 443 (M+Na), 438 (M+NH4), 421(M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=O.[CH3:14][C:15]1[N:16]=[C:17]([NH2:26])[S:18][C:19]=1[CH2:20][CH2:21][O:22][N+:23]([O-:25])=[O:24]>>[Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([NH:26][C:17]1[S:18][C:19]([CH2:20][CH2:21][O:22][N+:23]([O-:25])=[O:24])=[C:15]([CH3:14])[N:16]=1)=[O:8]
Reactant: Cc1nc(N)sc1CCO[N+](=O)[O-]
Reactant: O=C(O)COc1ccc(Cl)cc1Cl
Product: Cc1nc(NC(=O)COc2ccc(Cl)cc2Cl)sc1CCO[N+](=O)[O-]
Yield: 77 %

Procedure:
Pet-163 was prepared according to the general procedure described hereinabove and the procedure described above for the preparation of Pet-154, using (2,4-dichloro-phenoxy)-acetic acid and 4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-ylamine (Pet-10) as the starting materials, in an overall yield of 77%.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH2:24]([O:28][C:29](Cl)=[O:30])[CH2:25][CH2:26][CH3:27]>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([NH:16][C:29]([O:28][CH2:24][CH2:25][CH2:26][CH3:27])=[O:30])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC1CCN(C(=O)OCc2ccccc2)C1
Reactant: CCCCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCOC(=O)NC1CCN(C(=O)OCc2ccccc2)C1
Reaction time: 12 h

Procedure:
To a solution of 3.00 g 3-amino-pyrrolidine-1-carboxylic acid benzyl ester hydrotrifluoroacetate in 50 ml dichloromethane were added dropwise 3.7 ml triethylamine and 1.3 ml butylchloroformate at 0° C. After stirring for 12 h the reaction mixture was diluted with dichloromethane, washed with 0.1 M HCl, saturated aqueous NaHCO3 and brine. The crude product thus obtained was purified by flash chromatography on silica using ethyl acetate/heptane 2:3 as eluent. Yield: 648 mg.
Reaction SMILES: [Si:1]([O:8][C@H:9]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=1)[CH2:10][NH:11][C@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21](O)=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.[CH3:64][O:65][C:66]1[CH:73]=[CH:72][CH:71]=[C:70]([O:74][CH3:75])[C:67]=1[CH2:68][NH2:69]>CN(C)C=O>[NH3:11].[Si:1]([O:8][C@H:9]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=1)[CH2:10][NH:11][C@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21]([NH:69][CH2:68][C:67]2[C:70]([O:74][CH3:75])=[CH:71][CH:72]=[CH:73][C:66]=2[O:65][CH3:64])=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: C[C@H](Cc1cccc(CC(=O)O)c1)NC[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(O)c(CO)c1
Reactant: COc1cccc(OC)c1CN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cccc(OC)c1CNC(=O)Cc1cccc(C[C@@H](C)NC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(O)c(CO)c2)c1
Product: N
Temperature: 25 °C
Reaction time: 18 h
Yield: 128.4 %

Procedure:
A solution of (3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetic acid (Preparation 36) (150 mg, 0.32 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (67 mg, 0.35 mmol), hydroxybenzotriazole monohydrate (47 mg, 0.35 mmol) in N,N-dimethylformamide (3 ml) was treated with triethylamine (0.09 ml, 0.63 mmol) and 2,6-dimethoxybenzylamine (58 mg, 0.35 mmol) and the resulting suspension left to stir at room temperature under a nitrogen atmosphere for 18 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (10 ml) and saturated aqueous sodium bicarbonate (10 ml). The organic phase was separated, and the aqueous phase extracted with further ethyl acetate (2×10 ml). The combined organic extracts were washed with water (5 ml), brine (5 ml), dried (sodium sulphate) and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol: 880 ammonia (95:5:0.5 by volume) to give the title compound as a pale yellow oil (128 mg).
Reaction SMILES: Cl.[NH2:2][CH:3]([C:8]1[CH:16]=[CH:15][C:11]2[O:12][CH2:13][O:14][C:10]=2[CH:9]=1)[CH2:4][C:5]([OH:7])=[O:6].O.[C:18]1([CH2:24][C:25](Cl)=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CC(C)=O>[C:18]1([CH2:24][C:25]([NH:2][CH:3]([C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)[CH2:4][C:5]([OH:7])=[O:6])=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NC(CC(=O)O)c1ccc2c(c1)OCO2
Reactant: O=C(Cl)Cc1ccccc1
Agent: Cl
Solvent: CC(C)=O
Solvent: O
Product: O=C(O)CC(NC(=O)Cc1ccccc1)c1ccc2c(c1)OCO2
Temperature: -5 °C
Reaction time: 2 h

Procedure:
20 g of 3-amino-3-(benzo[1,3]dioxol-5-yl)propionic acid hydrochloride are placed in 10 ml of acetone, 30 ml of water and 38 ml of TEA at −5° C. and 14 ml of phenylacetyl chloride in 20 ml of acetone are added dropwise, followed by stirring for 2 hours at −5° C. The acetone is concentrated. The aqueous phase is washed with Et2O and the insoluble material is removed by filtration. The phases are separated again by settling and the aqueous phase is washed with Et2O and then acidified with 1N HCl to pH 2. The resulting phase is poured into DCM and a precipitate forms. The precipitate is filtered off by suction and rinsed with DCM. 24 g of the expected compound are obtained.
Reaction SMILES: [I-:1].C([N:9]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[CH:17]=[C:18]([CH2:45][CH3:46])[C:19]3[C:28]([CH:29]=2)=[S+:27][C:26]2[C:21](=[C:22]([CH3:44])[CH:23]=[C:24]([N:30]4[CH2:36][CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)[CH:25]=2)[N:20]=3)[CH2:11][CH2:10]1)(OC(C)(C)C)=O>ClCCl.FC(F)(F)C(O)=O>[I-:1].[N:12]1([C:16]2[CH:17]=[C:18]([CH2:45][CH3:46])[C:19]3[C:28]([CH:29]=2)=[S+:27][C:26]2[C:21](=[C:22]([CH3:44])[CH:23]=[C:24]([N:30]4[CH2:36][CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[CH:25]=2)[N:20]=3)[CH2:13][CH2:14][CH2:15][NH:9][CH2:10][CH2:11]1
Reactant: CCc1cc(N2CCCN(C(=O)OC(C)(C)C)CC2)cc2[s+]c3cc(N4CCCN(C(=O)OC(C)(C)C)CC4)cc(C)c3nc12
Agent: [I-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCc1cc(N2CCCNCC2)cc2[s+]c3cc(N4CCCNCC4)cc(C)c3nc12

Procedure:
a solution of 3,7-bis(4-Boc-1,4-diazepan-1-yl)-1-ethyl-9-methyl-phenothiazin-5-ium iodide (75 mg, 0.01 mmol) in dichloromethane (10 mL) and trifluoroacetic acid (1.0 mL) was stirred for 3 h at 50° C. The resulting mixture was washed by toluene (2×5 mL), pentane (2×5 mL) and concentrated to dryness.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1([CH2:16][S:17]([N:20]([C:22]2[CH:27]=[CH:26][C:25]([N:28]3[C:34](=[O:35])[CH2:33][C:32](=[O:36])[NH:31][C:30]4[C:37]5[C:42]([CH:43]=[CH:44][C:29]3=4)=[CH:41][CH:40]=[CH:39][CH:38]=5)=[CH:24][CH:23]=2)[CH3:21])(=[O:19])=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH2:11]1)([O-])=O.O.O.[Sn](Cl)Cl>ClCCl.C(OCC)(=O)C>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1([CH2:16][S:17]([N:20]([C:22]2[CH:27]=[CH:26][C:25]([N:28]3[C:34](=[O:35])[CH2:33][C:32](=[O:36])[NH:31][C:30]4[C:37]5[C:42]([CH:43]=[CH:44][C:29]3=4)=[CH:41][CH:40]=[CH:39][CH:38]=5)=[CH:24][CH:23]=2)[CH3:21])(=[O:19])=[O:18])[CH:11]=[CH:12][CH:13]=[CH:14][CH2:15]1
Reactant: CN(c1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1)S(=O)(=O)CC1(c2ccccc2[N+](=O)[O-])C=CC=CC1
Agent: Cl[Sn]Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CN(c1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1)S(=O)(=O)CC1(c2ccccc2N)C=CC=CC1
Temperature: 30 °C
Reaction time: 16 h
Yield: 72.5 %

Procedure:
1-(2-Nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide (33 mg, 0.062 mmol) mentioned above was dissolved in a mixed solvent of dichloromethane (0.5 mL) and ethyl acetate (1.5 mL), then the solution was added with tin(II) chloride dihydrate (70 mg, 0.310 mmol), and the mixture was stirred at 30° C. for 16 hours. After the disappearance of the starting materials was confirmed, the reaction mixture was treated in a conventional manner to give the title compound (26 mg, yield 31%) as white crystals.
Reaction SMILES: [CH2:1]([NH2:4])[C:2]#[CH:3].[C:5]12[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[NH:10]C(=O)[O:8][C:6]2=O>CN(C=O)C.O.C(Cl)Cl>[NH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:5]=1[C:6]([NH:4][CH2:1][C:2]#[CH:3])=[O:8]
Reactant: C#CCN
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Solvent: ClCCl
Solvent: O
Solvent: CN(C)C=O
Product: C#CCNC(=O)c1ccccc1N
Temperature: 45 °C
Reaction time: 16 h
Yield: 50.2 %

Procedure:
A solution of propargylamine (1.00 mL, 14.6 mmol) in DMF (4.0 mL) was added dropwise to a solution of isatoic anhydride (1.57 g, 9.72 mmol) in DMF (8.0 mL) at 45° C. The solution was stirred at 45° C. for 16 h and diluted with water and CH2Cl2. The aqueous phase was extracted with CH2Cl2 washed with water, brine, dried and concentrated. The crude product was recrystallised from EtOAc/petrol to give 2-amino-N-propargylbenzamide (0.85 g, 51%) as a colourless solid; mp 100-101° C., lit. [29] 98-100° C.; δH (400 MHz, DMSO-d6) 3.08 (t, J=2.4 Hz, 1H, C≡CH), 3.97 (dd, J=5.6, 2.4 Hz, 2H, CH2), 6.45 (s, 2H, NH2), 6.49 (t, J4,5=J5,6=7.8 Hz, 1H, H5), 6.68 (d, J3,4=7.8 Hz, 1H, H3), 7.13 (t, J3,4=J4,5=7.8 Hz, 1H, H4), 7.46 (d, J5,6=7.8 Hz, 1H, H6), 6.61 (t, J=5.6 Hz, 1H, NH).
Reaction SMILES: ON1C(=O)[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[O-:13]O.C1(C(C)C)C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:3]([O:12][OH:13])[C:4]1[CH:5]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: [O-]O
Reactant: O=C1c2ccccc2C(=O)N1O
Solvent: CC(C)c1ccccc1
Solvent: Cc1ccccc1
Product: OOCc1ccccc1
Reaction time: 8 h

Procedure:
0.3 mmol of N-hydroxyphthalimide and 0.6 mmol of cumene hydroperoxide are added at a temperature of 125° C. to 30 mmol of toluene in a round-bottomed flask having an attached reflux condenser. The reaction mixture is stirred for 8 hours at said temperature under an oxygen atmosphere of 1 bar. Benzyl hydroperoxide is obtained at a selectivity of 51.7% at a toluene conversion rate of 8%. Other products are benzaldehyde (24.6%) and benzoic acid (23.6%).