Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[C@@H:23]1[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25][CH2:24]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C>CN(C)C1C=CN=CC=1.ClCCCl>[Si:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[C@@H:23]1[CH2:24][CH2:25][C@H:26]([NH:29][S:31]([CH3:30])(=[O:33])=[O:32])[CH2:27][CH2:28]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc([C@H]2CC[C@@H](N)CC2)c(O[Si](C)(C)C(C)(C)C)c1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)Oc1ccc([C@H]2CC[C@@H](NS(C)(=O)=O)CC2)c(O[Si](C)(C)C(C)(C)C)c1
Reaction time: 17 h

Procedure:
A round bottomed flask equipped with magnetic stirrer was charged with cis-4-(2,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)cyclohexylamine (47 mg, 0.108 mmol) and 1,2-dichloroethane (4 ml). To the stirred solution was added methanesulfonyl chloride (10 μm, 0.12 mmol), triethylamine (30 μl, 0.22 mmol) and 4-dimethylaminopyridine (catalytic amount). The solution was stirred for 17 hr then partitioned between aqueous sodium hydroxide (5 ml, 0.2M) and dichloromethane (5 ml). The aqueous phase was extracted with dichloromethane (2×5 ml) and the combined organic layers were washed with brine (8 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was adsorbed onto silica gel and purified via flash column chromatography (SiO2, ethyl acetate/petroleum ether, gradient elution using 1:9, 1:4, then 1:3, v/v) to give the title compound (39 mg, 70%) which solidified on standing. δH(CDCl3) 0.17 (6H, s), 0.23 (6H, s), 0.97 (9H, s), 1.00 (9H, s), 1.53 (2H, m), 1.71 (4H, m), 1.94 (2H, m), 2.85 (1H, m), 2.99 (3H, s), 3.78 (1H, m), 4.83 (1H, d), 6.28 (1H, d), 6.42 (1H, dd), 6.97 (1H, d).
Reaction SMILES: [C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[O-]CC.[Na+].Br[C:12](=[N:17][NH:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:21][CH2:20]1)[C:13]([F:16])([F:15])[F:14]>CCO>[NH2:2][C:1]1[N:18]([CH:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:26])[CH2:23][CH2:24]2)[N:17]=[C:12]([C:13]([F:16])([F:15])[F:14])[C:3]=1[C:4](=[O:5])[NH2:6]
Reactant: O=C(OCc1ccccc1)N1CCC(NN=C(Br)C(F)(F)F)CC1
Reactant: N#CCC(N)=O
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: NC(=O)c1c(C(F)(F)F)nn(C2CCN(C(=O)OCc3ccccc3)CC2)c1N
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 38.5 %

Procedure:
To a stirred solution of 2-Cyanoacetamide (520 mg, 6.19 mmol) in EtOH (8.6 mL) at room temperature was added Sodium ethoxide (21% in EtOH, 1.6 mL, 4.13 mmol). A solution of 111 (842 mg, 2.063 mmol) in EtOH (1.7 mL) was added dropwise and the resulting suspension was allowed to stir for 10 min at room temperature, then for 2 h at 80° C. The solvent was removed and after the usual work-up the crude material was purified via Biotage (10% to 40% EtOAc/Hexane; 25S column) to give 117 (327 mg, 38.5% yield) as an orange solid. LRMS (ESI): calc.411.4; found 412.1 (MH)+.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[NH2:28]>>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[NH:28][C:2]1[C:3]2[C:8](=[N:7][C:6]([CH3:12])=[CH:5][CH:4]=2)[N:9]=[CH:10][CH:11]=1
Reactant: Cc1ccc(Sc2ccccc2F)c(N)c1
Reactant: Cc1ccc2c(Cl)ccnc2n1
Product: Cc1ccc(Sc2ccccc2F)c(Nc2ccnc3nc(C)ccc23)c1

Procedure:
The product from Example 1d (200 mg, 1.12 mmol) was reacted with the product from Example 89b (260 mg, 1.12 mmol) for 72 h following the procedure from Example 1g giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid (180 mg, 43%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 2.32 (s, 3H), 2.62 (s, 3H), 6.11 (br-s, 1H), 6.95-7.45 (m, 8H), 8.26 (br-s, 1H), 8.55-8.70 (m, 1H), 9.08 (br-s, 1H); MS (ESI+) m/z 376 (M+H)+, (ESI−) m/z 374 (M−H)−.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:10][CH2:11][C:12](=[O:19])[C:13]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].Cl[CH2:21][CH2:22][OH:23].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[OH:23][CH2:22][CH2:21][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:10][CH2:11][C:12](=[O:19])[C:13]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: CCOC(=O)C1=C(Nc2ccccc2O)OCC1=O
Reactant: OCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)C1=C(Nc2ccccc2OCCO)OCC1=O
Temperature: 90 °C
Reaction time: 48 h

Procedure:
A solution of ethyl 2-[(2-hydroxyphenyl)amino]-4-oxo-4,5-dihydrofuran-3-carboxylate (0.10 g, 0.38 mmol) which similarly prepared according to the procedure described in the Example 4, First step, 2-chloroethanol (0.038 mL, 0.57 mmol) and potassium carbonate (0.11 g, 0.80 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 90° C. for 2 days. Cooled to ambient temperature, ethyl acetate was added to the reaction mixture, the organic layer was washed with aqueous 5% citric acid solution, water and brine, dried over magnesium sulfate and concentrated. To the residue, tert-butyl methyl ether was added to precipitate the product. The precipitate was collected by filtration, washed with hexane then dried to afford ethyl 2-{[2-(2-hydroxyethoxy)phenyl]amino}-4-oxo-4,5-dihydrofuran-3-carboxylate as solid (0.041 g, y. 35%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:11]([C:14](=[CH2:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:12][CH3:13].N12CCCN=C1CCCCC2.O>CN(C=O)C.CCOC(C)=O>[CH2:18]([O:17][C:15](=[O:16])[CH:14]([CH2:20][NH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1)[CH2:11][CH2:12][CH3:13])[CH3:19]
Reactant: C=C(CCC)C(=O)OCC
Reactant: Nc1ncccc1[N+](=O)[O-]
Solvent: O
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: CCCC(CNc1ncccc1[N+](=O)[O-])C(=O)OCC
Temperature: 80 °C
Reaction time: 48 h
Yield: 11.4 %

Procedure:
To a stirred solution of 2-amino-3-nitropyridine (390 mg, 2.80 mmol) in DMF (3 ml) was added ethyl 2-propylacrylate (500 mg, 3.52 mmol) followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (30 μl). The mixture was warmed to 80° C. and monitored by TLC (silica gel, 30% EtOAc/hexanes). After 48 hours, only starting material was detected by TLC. The reaction mixture was warmed to 100° C. for 4 days and cooled to room temperature. The reaction was poured into water and EtOAc. The layers were separated and the aqueous phase was extracted once more with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated to give the crude product which was purified via silica gel flash column chromatography (Companion, 12 g silica gel, 15-50% EtOAc/hexanes). The product-containing fractions were combined and concentrated to give 90 mg (11%) of the desired compound which was used without further purification.
Reaction SMILES: [C:1]1([S:11]([O-:14])(=O)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Na+].P(Cl)(Cl)([Cl:18])=O.O>C(#N)C.CC(N(C)C)=O>[C:1]1([S:11]([Cl:18])(=[O:14])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)([O-])c1cccc2ccccc12
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Solvent: CC#N
Product: O=S(=O)(Cl)c1cccc2ccccc12
Temperature: 30 °C

Procedure:
133 g of sodium α-naphthalenesulfonate was suspended in a mixture of 260 ml of acetonitrile and 7 ml of dimethylacetamide. 80 ml of phosphorus oxychloride was added dropwise to the suspension while being cooled with water at a temperature of lower than 50° C. After the dropwise addition was completed, the reaction system was further reacted at a temperature of 65° C. for 1 hour. After cooled to 30° C., the reaction mixture was poured into 2 l of ice water. The resulting grayish white crystal was filtered off, and air-dried. The yield was 110.8 g (84.6% of theoretical value). The melting point of the product was 66° to 68° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Br:29][C:30]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][C:33]([NH2:34])=[C:32]([O:40][CH3:41])[CH:31]=1>CC(O)CCC>[Br:29][C:30]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][C:33]([NH:34][C:2]2[N:7]=[C:6]([C:8]3[CH:9]=[N:10][N:11]4[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)=[C:32]([O:40][CH3:41])[CH:31]=1
Reactant: COc1cc(Br)c([N+](=O)[O-])cc1N
Reactant: Clc1nccc(-c2cnn3c2CCCC3)n1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CCCC(C)O
Product: COc1cc(Br)c([N+](=O)[O-])cc1Nc1nccc(-c2cnn3c2CCCC3)n1
Yield: 58.7 %

Procedure:
A solution of 3-(2-chloropyrimidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (Intermediate 128, 0.893 g, 3.80 mmol), p-toluene sulphonic acid monohydrate (1.034 g, 5.43 mmol) and 4-bromo-2-methoxy-5-nitroaniline (Intermediate 4, 0.895 g, 3.62 mmol) in 2-pentanol (35 mL) was heated at reflux for 16 h under an atmosphere of N2. The mixture was then allowed to cool, and was concentrated in vacuo. The resulting residue was triturated in CH3CN until a yellow precipitate formed. The solid was collected by filtration and was washed with diethyl ether. The solid then was dissolved in 10% CH3OH in CH2Cl2 and the resulting solution was washed twice with sat. NaHCO3, then with water. The solution was then dried (MgSO4) and concentrated in vacuo. The resulting residue was triturated with CH3CN, the resulting solid collected by filtration, washed with diethyl ether, and then air dried to give the title compound (0.946 g, 59%) as a yellow solid; 1H NMR: 1.80-1.87 (2H, m), 1.96-2.03 (2H, m), 3.11 (2H, t), 4.04 (3H, s), 4.13 (2H, t), 7.17 (1H, d), 7.50 (1H, s), 8.13 (1H, s), 8.21 (1H, s), 8.45 (1H, d), 9.10 (1H, s); m/z: ES+ MH+ 445/447.
Reaction SMILES: [CH3:1][O:2][C:3]([CH3:8])([CH3:7])[C:4](O)=[O:5].C(N(CC)CC)C.[Cl-].C(OC(=O)O)C.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([S:30][C:31]2[N:36]=[C:35]([CH3:37])[CH:34]=[C:33]([CH3:38])[N:32]=2)=[CH:26][CH:25]=1.Cl>O1CCCC1.O>[CH3:1][O:2][C:3]([CH3:8])([CH3:7])[C:4]([NH:23][C:24]1[CH:25]=[CH:26][C:27]([S:30][C:31]2[N:32]=[C:33]([CH3:38])[CH:34]=[C:35]([CH3:37])[N:36]=2)=[CH:28][CH:29]=1)=[O:5]
Reactant: COC(C)(C)C(=O)O
Reactant: Cc1cc(C)nc(Sc2ccc(N)cc2)n1
Agent: CCOC(=O)O
Agent: Cl
Agent: [Cl-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(C)(C)C(=O)Nc1ccc(Sc2nc(C)cc(C)n2)cc1
Yield: 82.7 %

Procedure:
11.8 g (0.1 mole) of α-methoxy-isobutyric acid were dissolved in 150 ml of tetrahydrofuran, and 10.1 g (0.1 mole) of triethylamine were added. 10.85 g (0.1 mole) of carbonic acid ethyl ester-chloride were added dropwise at 10°-15° C., with stirring. The mixture was subsequently stirred at room temperature for 2 hours and 23.1 g (0.1 mole) of 2-(4-aminophenylmercapto)-4,6-dimethyl-pyrimidine were then added in portions. The mixture was subsequently stirred at room temperature for 1 hour and boiled under reflux for a further 2 hours. The reaction mixture was cooled and then stirred into one liter of water rendered slightly acid with hydrochloric acid. The crystals precipitated were filtered off with suction, washed with water and dried in air. 27.4 g (83% of theory) of 2-(4-(α-methoxy-isobutyrylamino)-phenylmercapto)-4,6-dimethyl-pyrimidine were obtained.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=2)[N:3]=1.[CH:16]([N:19]1[CH2:24][CH2:23][N:22]([C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:34]=[N:35][CH:36]=[C:37](B4OC(C)(C)C(C)(C)O4)[CH:38]=3)=[CH:29][CH:28]=2)=[O:26])[CH2:21][CH2:20]1)([CH3:18])[CH3:17]>>[Cl:8][C:6]1[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=2)[N:3]=[C:2]([C:37]2[CH:38]=[C:33]([C:30]3[CH:29]=[CH:28][C:27]([C:25]([N:22]4[CH2:21][CH2:20][N:19]([CH:16]([CH3:18])[CH3:17])[CH2:24][CH2:23]4)=[O:26])=[CH:32][CH:31]=3)[CH:34]=[N:35][CH:36]=2)[CH:7]=1
Reactant: Cc1cccc(-c2nc(Cl)cc(Cl)n2)n1
Reactant: CC(C)N1CCN(C(=O)c2ccc(-c3cncc(B4OC(C)(C)C(C)(C)O4)c3)cc2)CC1
Product: Cc1cccc(-c2nc(Cl)cc(-c3cncc(-c4ccc(C(=O)N5CCN(C(C)C)CC5)cc4)c3)n2)n1

Procedure:
This compound is prepared from 4,6-dichloro-2-(6-methyl-pyridin-2-yl)-pyrimidine (Int. B) and (4-isopropylpiperazin-1-yl)(4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)phenyl)methanone (Int. I) analogously to Example 1: [M+H]+=513/515 as a brown solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH:23]1([NH2:26])[CH2:25][CH2:24]1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([NH:26][CH:23]1[CH2:25][CH2:24]1)=[O:9]
Reactant: NC1CC1
Reactant: O=C(O)c1cc(Br)ccc1Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CC1)c1cc(Br)ccc1Cl
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a toluene solution (1 M) of 5-bromo-2-chlorobenzoic acid (1 eq.) and DMF (1.2 eq.) was added at 0° C. oxalyl chloride (1.2 eq.) dropwise over 1 h. The resulting solution was stirred at 0° C. for 2 h before the volatiles were removed in vacuo. The resulting residue was taken up in dichloromethane (1 M), cooled to 0° C. and added sequentially cyclopropylamine (1.5 eq.) and Hunig's base (2 eq.) dropwise over 1 h. The resulting suspension was stirred at RT for 18 h. The reaction was quenched with 1 N HCl and extracted with dichloromethane. The combined organic extracts were dried over MgSO4, filtered and the filtrate concentrated in vacuo to ˜⅓ in volume. The resulting white suspension was added an equivalent volume of hexanes and the title compound was isolated via vacuum filtration.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([CH:9]([CH3:11])[CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:13]1[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]2[S:21][CH:22]=[CH:23][CH:24]=2)[N:14]=1>C(O)CO.C(OCC)(=O)C>[Br:1][C:2]1[CH:8]=[C:7]([CH:9]([CH3:11])[CH3:10])[CH:6]=[CH:5][C:3]=1[NH:4][C:13]1[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]2[S:21][CH:22]=[CH:23][CH:24]=2)[N:14]=1
Reactant: CC(C)c1ccc(N)c(Br)c1
Reactant: Cc1cc(-c2cccs2)nc(Cl)n1
Solvent: CCOC(C)=O
Solvent: OCCO
Product: Cc1cc(-c2cccs2)nc(Nc2ccc(C(C)C)cc2Br)n1
Yield: 25.8 %

Procedure:
Part C: 2-Bromo-4-(1-methylethyl)aniline (0.26 g) and 2-chloro-4-methyl-6-(2-thienyl)pyrimidine (0.21 g) in ethylene glycol were heated at reflux for 24 hours. The reaction mixture was diluted with ethyl acetate, washed with aq. sodium hydroxide solution (10%, 3×100 mL) and the organic phase was dried. Solvent removal gave a crude brown oil, which was purified on silica gel using 20% ethyl acetate in hexanes (Rf 0.5) as eluent to provide N-(2-bromo-4-isopropylphenyl)-4-methyl-6-(2-thienyl)-2-pyrimidinamine (0.1 g) as a solid, mp 98-101° C. Mass spec (NH3 --CI/DDIP); 390 (M+H)+.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[C:22](Cl)(=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24]>ClCCl>[CH3:24][C:23]([CH3:26])([CH3:25])[C:22]([NH:15][C:12]1[CH:11]=[CH:10][C:9]([C:8]#[C:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:14][N:13]=1)=[O:27]
Reactant: Nc1ccc(C#Cc2ccccc2)cn1
Reactant: CC(C)(C)C(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)C(=O)Nc1ccc(C#Cc2ccccc2)cn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 43.5 %

Procedure:
(65 mg, 0.33 mmol) 5-Phenylethynyl-pyridin-2-ylamine (Example 1, step 1) was dissolved in dichloromethane (3 ml). Pyridine (52 mg, 53 μl, 0.67 mmol, 2 equiv.) and pivaloyl chloride (48 mg, 50 μl, 0.40 mmol, 1.2 equiv.) were added and the mixture was stirred for 2 hours at room temperature. The reaction mixture was extracted with 1N HCl solution and twice with dichloromethane. The organic extracts were combined, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with heptane:dichloromethane 50:50. The desired 2,2-dimethyl-N-(5-phenylethynyl-pyridin-2-yl)-propionamide (40 mg, 43% yield) was obtained as a light yellow solid, MS: m/e=279.3 (M+H+).
Reaction SMILES: [CH3:1][C:2]([CH3:56])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:55])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:54])=[CH:11]/[CH2:12][CH2:13]/[C:14](/[CH3:53])=[CH:15]/[CH2:16][CH2:17]/[C:18](/[CH3:52])=[CH:19]/[CH2:20][CH2:21]/[C:22](/[CH3:51])=[CH:23]/[CH2:24][CH2:25]/[C:26](/[CH3:50])=[CH:27]/[CH2:28][CH2:29]/[C:30](/[CH3:49])=[CH:31]/[CH2:32][CH2:33]/[C:34](/[CH3:48])=[CH:35]/[CH2:36][CH2:37]/[C:38](/[CH3:47])=[CH:39]/[CH2:40][CH2:41]/[C:42](/[CH3:46])=[CH:43]/[CH2:44][OH:45].[C:57](Cl)(=[O:64])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>N1C=CC=CC=1.CCCCCC>[C:57]([O:45][CH2:44][CH:43]=[C:42]([CH3:46])[CH2:41][CH2:40][CH:39]=[C:38]([CH3:47])[CH2:37][CH2:36][CH:35]=[C:34]([CH3:48])[CH2:33][CH2:32][CH:31]=[C:30]([CH3:49])[CH2:29][CH2:28][CH:27]=[C:26]([CH3:50])[CH2:25][CH2:24][CH:23]=[C:22]([CH3:51])[CH2:21][CH2:20][CH:19]=[C:18]([CH3:52])[CH2:17][CH2:16][CH:15]=[C:14]([CH3:53])[CH2:13][CH2:12][CH:11]=[C:10]([CH3:54])[CH2:9][CH2:8][CH:7]=[C:6]([CH3:55])[CH2:5][CH2:4][CH:3]=[C:2]([CH3:56])[CH3:1])(=[O:64])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CO
Solvent: c1ccncc1
Solvent: CCCCCC
Product: CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCOC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3.5 Grams of undecaprenol were dissolved in 30 ml of pyridine and the solution was added with a solution of 1.3 g of benzoyl chloride in pyridine dropwise over 30 minutes. After completion of the addition, the mixture was stirred at room temperature for one hour to complete the reaction. The reaction product was diluted with n-hexane, washed with water and concentrated. The concentrate was purified by chromatography with 50 g of silica gel in n-hexane/benzene solvent mixture as elution solvent to obtain white waxy final product. Yield: 3.6 g.______________________________________Elementary analysis as C62H94O2 : C H______________________________________Theoretical (%): 85.45 10.87Found (%): 85.43 10.86______________________________________
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21]2)=[CH:16][CH:15]=1.CCN(CC)CC>ClCCCl.CC(O)(C)C.CO.[Cl-].[Zn+2].[Cl-]>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH:20]3[CH2:21][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23]3)=[CH:18][CH:19]=2)[N:7]=1
Reactant: CC(C)(C)OC(=O)N1CC(c2ccc(N)cc2)C1
Reactant: FC(F)(F)c1cnc(Cl)nc1Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CO
Solvent: CC(C)(C)O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC(c2ccc(Nc3ncc(C(F)(F)F)c(Cl)n3)cc2)C1
Reaction time: 0.17 h

Procedure:
Zinc(II) chloride (1.0 M in Et2O; 4.83 mL, 4.83 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.769 g, 3.54 mmol) in DCE/t-BuOH (64 mL) at room temperature under nitrogen. After stirring for 10 minutes, tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate (A77) (0.800 g, 3.22 mmol) was added followed by Et3N (1.08 mL, 7.73 mmol). The resulting mixture was stirred at room temperature for 20 hours then the volatiles removed in vacuo. Water was added to the residue and the resulting suspension sonicated for 2 minutes. The suspension was filtered and the filter cake dried then adsorbed onto silica gel and purified using column chromatography (CombiFlash Rf, 40 g SiO2 cartridge, 10-40% EtOAc in cyclohexane) to give a white solid. The solid was suspended in MeOH (7 mL) and the resulting suspension sonicated for 30 seconds. The suspension was filtered and the filter cake washed with MeOH (3 mL), then dried to give the title compound A78 as a white solid (0.777 g, 56%); 1H NMR (300 MHz, d6-DMSO) δ 10.6 (s, 1H), 8.79 (s, 1H), 7.66 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz, 2H), 4.23 (t, J=7.6 Hz, 2H), 3.85-3.74 (m, 3H), 1.40 (s, 9H). LCMS-B: rt 8.810 min; m/z 429 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH:15]1([NH2:18])[CH2:17][CH2:16]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4]([NH:18][CH:15]1[CH2:17][CH2:16]1)=[O:5]
Reactant: NC1CC1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(F)cc1Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NC1CC1)c1cc([N+](=O)[O-])c(F)cc1Cl
Temperature: 0 °C
Reaction time: 2 h

Procedure:
2 g (9.11 mmol) of 2-chloro-4-fluoro-5-nitrobenzoic acid were dissolved in 91 g of dichloroethane, 22.66 g of thionyl chloride were added and the mixture was boiled until the evolution of gas had ended. The volatile constituents were distilled off and the acid chloride thus obtained was used directly in the next step. 2.166 g (9.1 mmol) of 2-chloro-4-fluoro-5-nitrobenzoyl chloride were dissolved in 100 ml of dichloromethane, this solution was cooled to 0° C., and 0.52 g (9.1 mmol) of cyclopropylamine and 1.38 g (13.65 mmol) of triethylamine were added together, predissolved in 5 ml of dichloromethane. After stirring at room temperature for two hours, the volatile constituents were distilled off, the resulting residue was slurried with a little diethyl ether, the diethyl ether phase was decanted off and the residue was stirred with water.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10](Br)[CH:11]=1)[NH:8][CH:7]=[CH:6]2.C(OC(=O)C=CC1C=CC=CN=1)C.[CH2:26]([O:28][C:29](=[O:49])[CH:30]=[C:31](C1C=CC=C2C=1C(C#N)=CN2)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:27]>>[CH2:26]([O:28][C:29](=[O:49])[CH:30]=[C:31]([C:10]1[CH:11]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:9]=1[NH:8][CH:7]=[CH:6]2)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:27]
Reactant: CCOC(=O)C=C(c1ccccc1)c1cccc2[nH]cc(C#N)c12
Reactant: COc1cc(Br)c2[nH]ccc2c1
Agent: CCOC(=O)C=Cc1ccccn1
Product: CCOC(=O)C=C(c1ccccc1)c1cc(OC)cc2cc[nH]c12

Procedure:
3-(5-Methoxy-1H-indol-7-yl)-3-phenyl-acrylic acid ethyl ester CLXXIX was prepared from 5-methoxy-7-bromo-1H-indole and 3-pyridin-2-yl-acrylic acid ethyl ester using the procedure described for preparation of 3-(3-Cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (Example 14).