Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([Cl:16])[C:11]=1[NH:12][C:13](=[O:15])[NH2:14])[CH:5]([OH:8])[CH2:6]Br.[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([Cl:16])[C:11]=1[NH:12][C:13](=[O:15])[NH:14][C:4]([CH3:9])([CH3:5])[CH3:3])[CH:5]([OH:8])[CH2:6][NH:21][C:17]([CH3:20])([CH3:19])[CH3:18]
Reactant: NC(=O)Nc1c(Cl)cc(C(O)CBr)cc1Cl
Reactant: CC(C)(C)N
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)(C)NCC(O)c1cc(Cl)c(NC(=O)NC(C)(C)C)c(Cl)c1
Reaction time: 0.5 h

Procedure:
A mixture of 0.86 g. of 3,5-dichloro-4-carbamoylamino-αbromomethylbenzyl alcohol and 10 ml. of tert-butylamine was heated to 90°-100° C. for 2 days in a sealed tube. After cooling the reaction mixture, the solvent was distilled off under reduced pressure and after adding to the residue formed 50 ml. of ethyl acetate, 50 ml. of water, and an excessive amount of sodium carbonate followed by stirring for 30 minutes, sodium chloride was added to the mixture until the mixture was saturated. Then, the mixture was separated into an ethyl acetate layer and an aqueous layer. The ethyl acetate layer formed was washed with a saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. Then, after filtering, the solvent was distilled off from the filtrate under reduced pressure. By recrystallizing the residue from ethyl acetate, 0.24 g. of 3,5-dichloro-4-tert-butylcarbamoylamino-α-(tert-butylaminomethyl)benzyl alcohol having a melting point of 167°-169° C. was obtained.
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH2:6][CH2:7][NH:8][CH2:9][C:10]1[S:14][C:13](B(O)O)=[CH:12][CH:11]=1)[CH2:2][CH3:3].Br[C:19]1[CH:20]=[C:21]2[C:25](=[C:26]([C:28]([NH2:30])=[O:29])[CH:27]=1)[NH:24][CH:23]=[C:22]2[CH:31]1[CH2:36][CH2:35][N:34]([S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])[CH2:33][CH2:32]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>[CH2:40]([S:37]([N:34]1[CH2:33][CH2:32][CH:31]([C:22]2[C:21]3[C:25](=[C:26]([C:28]([NH2:30])=[O:29])[CH:27]=[C:19]([C:13]4[S:14][C:10]([CH2:9][NH:8][CH2:7][CH2:6][CH2:5][O:4][CH2:1][CH2:2][CH3:3])=[CH:11][CH:12]=4)[CH:20]=3)[NH:24][CH:23]=2)[CH2:36][CH2:35]1)(=[O:39])=[O:38])[CH3:41]
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1
Reactant: CCCOCCCNCc1ccc(B(O)O)s1
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: [K+]
Product: CCCOCCCNCc1ccc(-c2cc(C(N)=O)c3[nH]cc(C4CCN(S(=O)(=O)CC)CC4)c3c2)s1
Yield: 2 %

Procedure:
Following the general procedure of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, (5-formyl-2-thienyl)boronic acid (50 mg, 0.32 mmol), [3-(propyloxy)propyl]amine (38 mg, 0.32 mmol), and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of crude [5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]boronic acid. The crude [5-({[3-(propyloxy)propyl]amino}methyl)-2-thienyl]boronic acid was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol), and tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.0079 mmol). The crude product was purified twice on an Agilent MDAP using the procedure shown in preparation of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide. The purified product was washed with a 20:4:1 mixture of hexaness/EtOAc/MeOH (2.5 mL), taken up in EtOAc (2 mL) and washed with saturated K2CO3 (1 mL). The organic layer was concentrated to give to give 1.4 mg of the title compound (2%).
Reaction SMILES: [CH:1]([C:4]1[C:9]([C:10](OCC)=[O:11])=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])[C:7]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])=[C:6]([CH:28]([CH3:30])[CH3:29])[N:5]=1)([CH3:3])[CH3:2]>C(OCC)(=O)C.CCCCCC>[CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])[C:7]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])=[C:6]([CH:28]([CH3:29])[CH3:30])[N:5]=1)([CH3:3])[CH3:2]
Reactant: CCCC=Cc1c(C(C)C)nc(C(C)C)c(C(=O)OCC)c1-c1ccc(Cl)cc1Cl
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCC=Cc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(Cl)cc1Cl

Procedure:
The title compound was prepared from the intermediate obtained in Step A by the procedure described in Example 125, Step F. 1H NMR (300 MHz, CDCl3) (reported as a 1:1 mixture of olefins): δ 0.75-0.87 (m, 3 H), 1.13-1.37 (m, 14 H), 1.65-2.0 (m, 2 H), 3.20-3.51 (m, 2 H), 4.30 (m, 1 H), 4.42 (m, 1 H), 5.31-5.50 (m, 1 H), 6.0 (m, 1 H), 7.05 (m, 1 H), 7.28 (m, 1 H), 7.47 (m, 1 H). Rf0.38 (10% ethyl acetate/n-hexane).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[CH:6]=1.[Li]CCCC.[Si:13]([O:20][CH2:21]/[CH:22]=[N:23]/[S:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>CCOCC.C(Cl)Cl>[Br:7][C:5]1[CH:6]=[C:2]([CH:22]([NH:23][S:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH2:21][O:20][Si:13]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:15])[CH3:14])[S:3][CH:4]=1
Reactant: Brc1csc(Br)c1
Reactant: CC(C)(C)S(=O)/N=C/CO[Si](C)(C)C(C)(C)C
Agent: [Li]CCCC
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)(C)S(=O)NC(CO[Si](C)(C)C(C)(C)C)c1cc(Br)cs1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2,4-dibromothiophene (3.49 g, 14.41 mmol) was dissolved in Et2O (120 mL) at −78° C., and then n-BuLi (4.32 mL of 2.5 M, 10.8 mmol) was added dropwise and the resulting mixture was stirred for 30 minutes. This solution was cannulated into a solution of N-[(1E)-2-{[tert-butyl(dimethyl)silyl]oxy}ethylidene]-2-methylpropane-2-sulfinamide (2 g, 7.21 mmol) in 120 mL DCM at −78° C. The reaction mixture was quenched with aqueous ammonium chloride and warmed to room temperature. The mixture was extracted with ethyl acetate (3×) and the combined organic fractions were washed with brine, dried (MgSO4), and filtered. The ethyl acetate solvent was then evaporated under reduced pressure, and the resulting product purified on silica gel (EtOAc/hexanes) to give the title compound.
Reaction SMILES: C[O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[NH:14])[NH:12][OH:13])=[CH:7][CH:6]=1>Cl>[OH:13][NH:12][C:11]([C:8]1[CH:7]=[CH:6][C:5]([CH2:4][C:3]([OH:15])=[O:2])=[CH:10][CH:9]=1)=[NH:14]
Reactant: COC(=O)Cc1ccc(C(=N)NO)cc1
Agent: Cl
Product: N=C(NO)c1ccc(CC(=O)O)cc1
Yield: 107.2 %

Procedure:
A solution of the above [4-(N-hydroxycarbamimidoyl)-phenyl]-acetic acid methyl ester (2.0 g, 9.61 mmol) in 2 M aq. HCl is stirred at 65° C. for 16 h, then at 80° C. for 24 h before it is concentrated and dried to give sufficiently pure title compound (2.0 g) as a white solid; LC-MS: tR=0.34 min, [M+1]+=195.07.
Reaction SMILES: [CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([O:10][C:11](/[CH:13]=[CH:14]/[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=O)C>O1CCCC1>[CH3:4][O:3][P:2]([CH2:1][C:11](=[O:10])/[CH:13]=[CH:14]/[CH:15]1[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:19][CH2:20]1)([O:5][CH3:6])=[O:7]
Reactant: CCOC(=O)/C=C/C1CCN(C(=O)OC(C)(C)C)CC1
Reactant: COP(C)(=O)OC
Solvent: C1CCOC1
Product: COP(=O)(CC(=O)/C=C/C1CCN(C(=O)OC(C)(C)C)CC1)OC
Reaction time: 0.17 h

Procedure:
To a solution of 13.1 g (106 mM) of dimethyl methylphosphonate in 100 ml of tetrahydrofuran was added 69.2 ml (111 mM) of 1.6M n-butyllithium-hexane dropwise at −78° C. and the mixture was stirred at the prevailing temperature for 10 minutes. To this reaction mixture was added a solution of 14.271 g (50.362 mM) of tert-butyl (E)-4-(2-ethoxycarbonylvinyl)piperidine-1-carboxylate in 100 ml of tetrahydrofuran at −78° C. and the mixture was stirred until the temperature had recovered to room temperature. This reaction mixture was poured in aqueous solution of ammonium chloride and extracted with 3 portions of ethyl acetate. The organic layers were pooled and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate:1/1 to ethyl acetate) to provide the title compound.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1.[CH:11]([Si:13]([Cl:16])([Cl:15])[Cl:14])=[CH2:12]>[Cl-].[Al+3].[Cl-].[Cl-]>[Cl:14][Si:13]([CH2:11][CH2:12][C:10]1[C:5]([CH2:4][CH2:3][CH2:2][CH3:1])=[C:6]([CH2:12][CH2:11][Si:13]([Cl:16])([Cl:15])[Cl:14])[C:7]([CH2:12][CH2:11][Si:13]([Cl:16])([Cl:15])[Cl:14])=[C:8]([CH2:12][CH2:11][Si:13]([Cl:16])([Cl:15])[Cl:14])[C:9]=1[CH2:12][CH2:11][Si:13]([Cl:16])([Cl:15])[Cl:14])([Cl:16])[Cl:15]
Reactant: C=C[Si](Cl)(Cl)Cl
Reactant: CCCCc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Product: CCCCc1c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c1CC[Si](Cl)(Cl)Cl
Yield: 102.2 %

Procedure:
In the same apparatus and by the same procedure described in EXAMPLE 1, n-butylbenzene 0.86 g (6.40 mmol), vinyltrichlorosilane 5.17 g (32.00 mmol) and aluminum chloride 0.047 g (0.35 mmol) were reacted at 80° C. for 6 hours under a dry nitrogen atmosphere. Recrystallization of solid product from THF gave 6.16 g (yield: 2.68%, mp: 228°-35° C.) of pentakis(trichlorosilylethyl)-n-butylbenzene. Distillation of the filtrate gave 2.20 g (yield: 36.59%, bp: 192°-8° C./0.6 mm), 1.81 g (yield: 30.0%, bp: 220°-5° C./0-6 mm), 0.63 g (yield: 10.15%), 0.12 g (yield: 2.05%) and 0.22 g (yield: 3.59%) of tris-, tetrakis(trichlorosilylethyl)-n-butylbenzenes, tetrakis(trichlorosilylethyl)dibutylbenzene, mono- and bis(trichlorosilylethyl)benzenes, respectively. isomeric mixtures were also obtained. NMR data of the polyalkylated products prepared as above are listed in Table 13.
Reaction SMILES: [CH3:1][N:2]([CH3:17])[CH:3]1[CH2:15][C:14]2[C:13]3[C:8](=[C:9](Br)[CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[CH2:5][CH2:4]1.[CH3:18][N:19](C)C=O.C(N)CN>O>[CH3:1][N:2]([CH3:17])[CH:3]1[CH2:15][C:14]2[C:13]3[C:8](=[C:9]([C:18]#[N:19])[CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[CH2:5][CH2:4]1
Reactant: CN(C)C1CCc2[nH]c3c(Br)cccc3c2C1
Reactant: CN(C)C=O
Solvent: NCCN
Solvent: O
Product: CN(C)C1CCc2[nH]c3c(C#N)cccc3c2C1

Procedure:
3-(Dimethylamino)-8-bromo-1,2,3,4-tetrahydrocarbazole (18.8 g.)(Example 211) and 17.5 g. of cuprous cyanide in 150 ml. of dimethylformamide was heated under reflux for four hours. The warm reaction mixture was poured into a solution of 200 ml. of ethylenediamine in 400 ml. of water. This was mixed thoroughly and extracted several times with chloroform. The chloroform layer was separated and washed with a dilute solution of ethylenediamine, water, saturated salt solution, and evaporated to dryness to give, after recrystallization from benzene, 6.9 g. of 3-(dimethylamino)-8-cyano-1,2,3,4-tetrahydrocarbazole, m.p. 177°-179° C.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[CH:8](I)([CH3:10])[CH3:9]>C(O)C>[CH:8]([S:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1)([CH3:10])[CH3:9]
Reactant: CC(C)I
Reactant: Sc1ccncc1
Solvent: CCO
Product: CC(C)Sc1ccncc1

Procedure:
A mixture of 4-mercaptopyridine (555 mg, 5 mmoles) and isopropyl iodide (0.50 ml) in ethanol (5 ml) was heated under reflux for 4 hours and then evaporated under reduced pressure. The residue was dissolved in a small amount of water, made alkaline with aqueous sodium hydroxide and extracted with ethyl acetate. The extract was washed with a small amount of water, dried and evaporated under reduced pressure to give the product as an oil. Yield, 670 mg (88%).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=3)[N:18]=2)=[CH:13][CH:12]=1.[OH-].[Na+]>C(O)C.O1CCCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[CH:30][CH:31]=3)[N:18]=2)=[CH:13][CH:12]=1
Reactant: COCCCCCCCOc1ccc(-c2nc(-c3ccc(C(=O)OC)cc3)no2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: COCCCCCCCOc1ccc(-c2nc(-c3ccc(C(=O)O)cc3)no2)cc1
Temperature: 65 °C
Reaction time: 2 h
Yield: 84.3 %

Procedure:
A mixture of methyl 4-[5-[4-(7-methoxy-n-heptyloxy)phenyl]-1,2,4-oxadiazol-3-yl]benzoate (5.4 g) and 10% sodium hydroxide aqueous solution (15 ml) in ethanol (60 ml) and tetrahydrofuran (30 ml) was stirred at 60-70° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and water added to the residue and adjusted to pH 1 using hydrochloric acid. The precipitates were collected by filtration, washed with water and dried in vacuo to give 4-[5-[4-(7-methoxy-n-heptyloxy)phenyl]-1,2,4-oxadiazol-3-yl]benzoic acid (4.4 g).
Reaction SMILES: [Cl:1][C:2]1[C:10]([O:11][CH:12]([CH3:14])[CH3:13])=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:15][CH:16]([CH3:18])[CH3:17].CCN(C(C)C)C(C)C.[NH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1>>[Cl:1][C:2]1[C:3]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:4][C:5]([C:6]([NH:28][C:29]2[CH:30]=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][CH:38]=2)=[O:8])=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]
Reactant: COC(=O)c1ccc(N)cc1
Reactant: CC(C)Oc1cc(C(=O)O)cc(OC(C)C)c1Cl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(NC(=O)c2cc(OC(C)C)c(Cl)c(OC(C)C)c2)cc1
Yield: 96 %

Procedure:
Methyl 4-(4-chloro-3,5-diisopropoxybenzamido)benzoate (8) (86 mg, 96%) was prepared from 4-chloro-3,5-diisopropoxybenzoic acid (6) (60 mg, 0.22 mmol) using a procedure essentially the same as in step (i) for AAA-064 except that DIPEA was used instead of TEA, and methyl 4-aminobenzoate was used instead of methyl 4-amino-2-fluorobenzoate: m/z 406 [M+H]+ (ES)+, 404 [M−H]− (ES)−.
Reaction SMILES: [CH2:1]([N:4]1[CH2:10][CH2:9][C:8]2[CH:11]=[C:12]([NH2:15])[CH:13]=[CH:14][C:7]=2[CH2:6][CH2:5]1)[C:2]#[CH:3].Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:26][C:25]=2[O:36][CH3:37])[C:20]([Cl:38])=[CH:19][N:18]=1>>[Cl:38][C:20]1[C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[CH:26][C:25]=2[O:36][CH3:37])=[N:22][C:17]([NH:15][C:12]2[CH:13]=[CH:14][C:7]3[CH2:6][CH2:5][N:4]([CH2:1][C:2]#[CH:3])[CH2:10][CH2:9][C:8]=3[CH:11]=2)=[N:18][CH:19]=1
Reactant: COc1cc(N2CCOCC2)ccc1Nc1nc(Cl)ncc1Cl
Reactant: C#CCN1CCc2ccc(N)cc2CC1
Product: C#CCN1CCc2ccc(Nc3ncc(Cl)c(Nc4ccc(N5CCOCC5)cc4OC)n3)cc2CC1

Procedure:
5-Chloro-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-N*2*-(3-prop-2-ynyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-pyrimidine-2,4-diamine was prepared from 3-prop-2-ynyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and (2,5-dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine in an analogous manner to Example 322. Product isolated as a pale yellow solid (120 mg, 46%). m.p.=151-152° C.; LCMS (m/e) 519 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.27 (d, 1H, J=8.7 Hz), 8.02 (s, 1H), 7.61 (s, 1H), 7.48 (s, 1H), 7.23-7.16 (m, 1H), 7.04 (d, 1H, J=8.0 Hz), 6.89 (s, 1H), 6.56 (s, 1H), 6.55-6.49 (m, 1H), 3.94 (s, 3H), 3.91 (m, 4H,), 3.45 (s, 2H), 3.21-3.15 (m, 4H), 2.98-2.89 (m, 4H), 2.82-2.70 (m, 4H), 2.25-2.21 (m, 1H).
Reaction SMILES: C(N(CC)CC)C.[Cl-].[CH2:9]([O:11][C:12]1([NH3+:15])[CH2:14][CH2:13]1)[CH3:10].[C:16](Cl)(=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>O1CCCC1>[CH2:9]([O:11][C:12]1([NH:15][C:16](=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:13]1)[CH3:10]
Reactant: CCCCCC(=O)Cl
Reactant: CCOC1([NH3+])CC1
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCC(=O)NC1(OCC)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Triethylamine (2.22 g, 22 mmol) is added dropwise (15 min) with vigorous stirring at 0° to a solution of 1-ethoxycyclopropylammonium chloride (1.37 g, 10 mmol) and caproyl chloride (1.34 g, 10 mmol) in dry tetrahydrofuran (30 ml) and the mixture is stirred at room temperature for 1 hr. The precipitate is filtered off and the filtrate is evaporated in vacuo. The crystalline residue (1.85 g) is dissolved in petroleum ether (20 ml) and the solution is filtered through a short silica-gel column (2 cm × 10 cm). After evaporation the residue (1.30 g) is recrystallised from petroleum ether (at low temperature) yielding pure N-(1-ethoxycyclopropyl)-caproic amide, mp 47°-48.5° (1.0 g, 50%); NMR (60 MHz): δCDCl 3 = 0.7-1.9 (m, 16H), 2.0-2.4 and 2.4-2.8 (2 m, total 2H), 3,57 and 3.63 (2q, J=7.2 Hz, total 2H), 6.7 (br. s, 1H), (two rotamers).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]2[C:9](=[O:25])[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)[CH:7]=1.[CH:27]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]2[C:9](=[O:25])[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([CH3:27])[CH:12]=3)[CH:7]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Cc1ccc(N)cc1-c1cc2cnc(Cl)cc2n(-c2ccccc2)c1=O
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: Cc1cc2c(cn1)cc(-c1cc(N)ccc1C)c(=O)n2-c1ccccc1
Temperature: 140 °C

Procedure:
A vial is charged with 19 (208 mg, 0.575 mmol), Pd2(dba)3 (26 mg, 0.028 mmol) and Ph3P (37 mg, 0.14 mmol). The vial is evacuated and refilled with N2. Dioxane (12 mL) is added to the vial and the solution is treated with AlMe3 (0.86 mL of a 2M solution in hexane, 1.72 mmol). The mixture is heated in a microwave oven at 140° C. for 20 min. The vial is cooled down to rt and the mixture is extracted with ethyl acetate. The organic phase is washed with 1N NaOH solution, saturated NaHCO3 solution and brine. The solvent is removed in vacuo and the crude product is purified using flash chromatography (hexane:ethyl acetate=2:1) to give 3-(5-amino-2-methyl-phenyl)-7-methyl-1-phenyl-1H-[1,6]naphthyridin-2-one 20. 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.75 (s, 1H), 7.58-7.63 (m, 2H), 7.52-7.56 (m, 1H), 7.28-7.30 (m, 2H), 7.03 (d, 1H), 6.67 (d, 1H), 6.64 (d, 1H), 6.38 (s, 1H), 5.32 (s, 1H), 3.60 (brs, 2H), 2.46 (s, 3H), 2.18 (s, 3H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH:9]=[C:8]2[CH2:24][CH2:25][N:26]1C(=O)C2C(=CC=CC=2)C1=O)[CH2:2][CH3:3]>CCO.O.NN>[CH2:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11]([N:10]([Si:14]([CH:21]([CH3:22])[CH3:23])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:16])[CH3:17])[CH:9]=[C:8]2[CH2:24][CH2:25][NH2:26])=[CH:12][CH:13]=1)[CH2:2][CH3:3]
Reactant: CCCOc1ccc2c(c1)c(CCN1C(=O)c3ccccc3C1=O)cn2[Si](C(C)C)(C(C)C)C(C)C
Agent: NN
Solvent: O
Solvent: CCO
Product: CCCOc1ccc2c(c1)c(CCN)cn2[Si](C(C)C)(C(C)C)C(C)C

Procedure:
Combine 2-(2-(5-propoxy-1-triisopropylsilanyl-1H-indol-3-yl)ethyl)isoindole-1,3-dione (416 mg, 0.8 mmol) in 20 mL EtOH and 1 mL hydrazine hydrate. Reflux for 3 hours, filter through celite and concentrate to residue. Dissolve the residue in 10 mL MeOH and load onto a 12 g SCX ion exchange cartridge and rinse sequentially with MeOH, DMP, then MeOH. Elute the product with 2 M NH3 in MeOH to give the title compound as an oil: ISMS 375 (M+1); 1H NMR (CDCl3) 7.34–7.32 (d, 1H), 7.02 (s, 1H), 7.00–6.99 (d, 1H), 6.80–6.77 (m, 1H), 3.97–3.94 (m, 2H), 3.01–2.98 (m, 2H), 2.86–2.83 (m, 2H), 1.88–1.76 (m 2H), 1.70–1.58 (m, 3H), 1.3 (bs, 2H), 1.14–1.08 (m, 18H), 1.06–1.02 (t, 3H).
Reaction SMILES: O.[C:2]1([C:8]([CH:10]=[O:11])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1>ClC(Cl)C.[Ti](Cl)(Cl)(Cl)Cl>[CH2:14]([C:15]1[CH:16]=[CH:17][C:18]([CH:10]([OH:11])[C:8](=[O:9])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:19][CH:20]=1)[CH2:13][CH3:12]
Reactant: O=CC(=O)c1ccccc1
Reactant: CCCc1ccccc1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: CC(Cl)Cl
Solvent: O
Product: CCCc1ccc(C(O)C(=O)c2ccccc2)cc1

Procedure:
Phenylglyoxal monohydrate (304 mg, 2 mM) and n-propylbenzene (0.56 ml, 4 mM) were dissolved in dichloroethane (6 ml), titanium tetrachloride (0.33 ml, 3 mM) was added, and reacted at room temperature for 2 hours. Using the same procedure as in Example 1, 4'-n-propylbenzoin was obtained as crystal (369.9 mg, 71.9% yield).
Reaction SMILES: [C:1]([O:4][C:5]1[C:10]([CH3:11])=[C:9]([CH3:12])[C:8]([O:13][C:14](=[O:16])[CH3:15])=[C:7]([CH3:17])[C:6]=1[CH2:18][CH:19]=O)(=[O:3])[CH3:2].[C:21]([CH:26]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:23][CH2:24][CH3:25])=[O:22]>>[C:1]([O:4][C:5]1[C:10]([CH3:11])=[C:9]([CH3:12])[C:8]([O:13][C:14](=[O:16])[CH3:15])=[C:7]([CH3:17])[C:6]=1[CH2:18]/[CH:19]=[CH:26]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])(=[O:3])[CH3:2]
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(=O)Oc1c(C)c(C)c(OC(C)=O)c(CC=O)c1C
Product: CCOC(=O)/C=C/Cc1c(C)c(OC(C)=O)c(C)c(C)c1OC(C)=O

Procedure:
In the first step a condensation according to Wittig is carried out between 2,5-diacetyloxy-3,4,6-trimethylphenylacetaldehyde and carboethoxymethylentriphenylphosphorane, dissolving the two compounds in a suitable organic solvent under stirring, bringing then the solution to boil and refluxing it for a sufficiently long time. By evaporation of the solvent, ethyl trans-4-(2,5-diacetyloxy-3,4,6-trimethylphenyl)-2-butenoate is obtained, which is crystallized by a suitable solvent.