Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]([N:17]1[CH2:22][CH2:21][C:20](=[C:23]2[C:29]3[CH:30]=CC=C[C:28]=3[CH:27]=[CH:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]2=3)[CH2:19][CH2:18]1)=[O:16])[C:10](OC)=[O:11])=O)(C)(C)C>C(O)C.[H][H].[C].[Pd]>[CH:10]1[C:28]2[CH2:27][CH2:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]=3[C:23](=[C:20]3[CH2:19][CH2:18][N:17]([C:15](=[O:16])[CH2:14][C@@H:9]([NH:8][C:6](=[O:5])[C:20]([CH3:23])([CH3:21])[CH3:19])[CH2:10][OH:11])[CH2:22][CH2:21]3)[C:29]=2[CH:30]=[CH:14][CH:9]=1
Reactant: COC(=O)[C@@H](CC(=O)N1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1)NC(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)C(=O)N[C@@H](CO)CC(=O)N1CCC(=C2c3ccccc3CCc3ccccc32)CC1

Procedure:
745 mg (1.48 mmol) of methyl (R)-2-[(t-butoxycarbonyl)amino]-4-[4-(5H-dibenzo[a,d] [7]annulen-5-ylidene)-1-piperidinyl]-4-oxobutanoate was dissolved in 70 ml of ethanol. 1.49 g of palladium carbon (10% w/v) was added to the obtained solution, and they were stirred at room temperature in hydrogen gas atmosphere under 4.4 atm. for 3.5 hours. The catalyst was filtered out, and the filtrate was concentrated under reduced pressure. The intended product was obtained from the resultant residue in the same manner as that in steps 3 and 4 in Referential Example 50.
Reaction SMILES: Br.[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([OH:10])=O)[N:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:35][CH:36]1[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[O:10])[N:7]=1
Reactant: Nc1nc(C(=O)O)cs1
Reactant: CN1CCC(N)CC1
Agent: Br
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN1CCC(NC(=O)c2csc(N)n2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.6 %

Procedure:
2-Aminothiazole-4-carboxylate hydrobromide salt (Chempacific; 1.13 g, 5.02 mmol), HATU (2.87 g, 7.53 mmol) and 4-amino-1-methylpiperidine (0.86 g, 7.53 mmol) were stirred in DMF (5 mL) and DIPEA (5.2 mL, 30.12 mmol) added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue taken up in methanol, absorbed onto an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined, evaporated and the residue and further purified by column chromatography (5% 7N NH3 in MeOH/DCM) Product containing fractions were combined and evaporated to give the title compound as a yellow solid (635 mg, 53%).
Reaction SMILES: [OH:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[CH3:16]O>>[CH3:16][O:9][C:8](=[O:10])[C:3]1[C:2]([OH:1])=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: CO
Reactant: O=C(O)c1ncccc1O
Agent: O=S(=O)(O)O
Product: COC(=O)c1ncccc1O

Procedure:
To a stirred solution of 3-hydroxypicolinic acid (0.7122g, 5.1 mmol) in CH3OH (32 mL) at room temperature was added concentrated H2SO4 (4 mL). The mixture was heated to reflux for 18 hrs then concentrated. The residue was diluted with saturated aqueous Na2CO3 (45 mL) and extracted with CH2Cl2 (4×30 mL). The combined organic phases were dried (Na2SO4) and concentrated to give 0.73 g 3-hydroxypicolinic acid methyl ester as a white powder.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]([C:19]([O:21][CH3:22])=[O:20])[C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]([N-]C(C)C)([CH3:25])[CH3:24].[Li+].C(Br)C=C>C1COCC1>[CH2:25]([C:14]([C:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:9][CH:10]=1)([C:19]([O:21][CH3:22])=[O:20])[C:15]([O:17][CH3:18])=[O:16])[CH:23]=[CH2:24]
Reactant: CC(C)[N-]C(C)C
Reactant: COC(=O)C(C(=O)OC)c1ccc(Oc2ccccc2)cc1
Agent: [Li+]
Solvent: C1CCOC1
Solvent: C=CCBr
Product: C=CCC(C(=O)OC)(C(=O)OC)c1ccc(Oc2ccccc2)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution of dimethyl 2-(4-phenoxyphenyl)malonate (2.56 g, 8.54 mmol) in dry THF (50 mL) was cooled to −78° C. and then lithium diisopropylamide (4.7 mL of a 2M solution in ThF, 9.8 mmol) was added. The reaction was stirred at −78° C. for 1 hour and then allyl bromide (11.4 mg, 9.4 mmol) was added. The reaction was stirred at −78° C. for 3 hours and then allowed to warm to room temperature and heated in a 75° C. oil bath until the reaction was shown to be complete by TLC. The reaction was cooled to room temperature and quenched with 1N HCl. Extraction with ether and drying of the ether extracts (MgSO4) gave crude product. Purification by filtration through silica gel 60 (70-230 mesh) using EtOAc, followed by HPLC (porasil) using 11% EtOAc/hexanes gave 1.8 g of dimethyl 2-(2-propenyl)-2-(4-phenoxyphenyl)malonate as a viscous oil: 1H NMR (200 mHz, CDCl3) δ 7.4-6.85 (9H, m), 5.75 (1H, m), 5.05 (2H, m), 3.75 (6H, s), 3.1 (2H, d).
Reaction SMILES: [CH3:1][SiH:2]([CH3:6])[O:3][CH2:4][CH3:5].[Br:7][CH2:8][CH2:9][CH:10]=[CH2:11]>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Ru].[Ru].[Ru]>[Br:7][CH2:8][CH2:9][CH2:10][CH2:11][Si:2]([CH3:6])([CH3:1])[O:3][CH2:4][CH3:5]
Reactant: CCO[SiH](C)C
Reactant: C=CCCBr
Agent: [Ru]
Agent: [C-]#[O+]
Product: CCO[Si](C)(C)CCCCBr
Temperature: 80 °C

Procedure:
800 g of 4-bromo-1-butene were reacted with 15% excess of dimethylethoxysilane (939 ml). In a 2 l reactor 0.5 g of Ru3(CO)12 and 800 ml of 4-bromo-1-butene were brought under nitrogen and 939 ml of dimethylethoxysilane were added under nitrogen and the mixture was brought at 65° C. After 0.5 h the bath temperature was raised to 80° C. and the mixture was allowed to react overnight. After distillation 1329 g (93.7%) of 4-bromobutyl-dimethyl-ethoxysilane were isolated.
Reaction SMILES: [OH:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[CH:3]=1.[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17](O)[CH2:16]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.ClCCl>[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17]([O:1][C:2]1[CH:14]=[CH:13][C:12]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[NH:5][C:4]=3[CH:3]=1)[CH2:16]2
Reactant: Oc1ccc2c(c1)[nH]c1ccccc12
Reactant: OC1CN2CCC1CC2
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: c1ccc2c(c1)[nH]c1cc(OC3CN4CCC3CC4)ccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.4 %

Procedure:
To a 0° C. mixture of 2-hydroxy-9H-carbazole (369 mg, 2.02 mmol; Aldrich), quinuclidin-3-ol (260 mg, 2.05 mmol; Aldrich), and triphenylphosphine (646 mg, 2.47 mmol; Aldrich) in THF (10 mL) was added diethylazodicarboxylate (320 μL, 2.03 mmol; Lancaster). After 1 h, the reaction mixture was allowed to warm to room temperature and was stirred for 3 d. The mixture was diluted with dichloromethane, washed with saturated aq. NaHCO3, dried over MgSO4, and purified by flash chromatography (80 g silica gel, eluting with 1-16% of 10% NH4OH/MeOH in CH2Cl2) to afford the title compound as an oil (350 mg, 1.20 mmol, 59% yield). Trituration of the oil with ethyl acetate produced a solid. 1H NMR (300 MHz, methanol-d4) δ 7.92 (1H, d, J=6 Hz), 7.90 (1H, d, J=8 Hz), 7.37 (1H, d, J=8 Hz), 7.26 (1H, ddd, J=7, 7, 1 Hz), 7.10 (1H, ddd, J=8, 8 ,1 Hz), 6.92 (1H, d, J=2 Hz), 6.78 (1H, dd, J=8, 2 Hz), 4.59 (1H, m), 3.36 (1H, ddd, J=14, 8, 2 Hz), 3.04-2.75 (5H, m), 2.22 (1H, m), 2.11 (1H, m), 1.88-1.65 (2H, m), 1.51 (1H, m). MS (DCl/NH3): m/z 293 (M+1)+. Anal. Calcd. for C19H20N2O.0.1C4H8O2: C, 77.36; H, 6.96; N, 9.30. Found: C, 77.04; H, 7.23; N, 9.45.
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[OH-].[Na+].[C:14]([O:18][CH3:19])(=[O:17])[CH:15]=[CH2:16]>C1COCC1>[O:11]=[C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:16][CH2:15][C:14]([O:18][CH3:19])=[O:17]
Reactant: C=CC(=O)OC
Reactant: O=C1NCCc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COC(=O)CCN1CCc2ccccc2C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 66.8 %

Procedure:
Dissolve 3,4-dihydroisoquinolin-1(2H)-one (500 mg, 3.40 mmol) in THF (20 mL) and add sodium hydroxide (274.5 mg, 6.79 mmol) followed by methyl acrylate (438.7 mg, 5.10 mmol) in THF (1 mL). Stir the mixture at ambient temperature for 3 hours; quench with water (20 mL); and then dilute with EtOAc (100 mL). Wash the resulting mixture with brine; dry the organic phase over Na2SO4; filter; and concentrate the filtrate under reduced pressure to provide the title compound as a yellow oil (530 mg, 66.9%). MS (m/z): 234 (M+1).
Reaction SMILES: [C:1]([NH:4][C@H:5]([C:13]([OH:15])=O)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:3])[CH3:2].Cl.Cl.[CH2:18]([O:20][C:21](=[O:31])[C@H:22]([CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:30])[NH2:29])[NH2:23])[CH3:19].C(N(CC)CC)C.ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[CH3:19][CH2:18][O:20][C:21]([C@@H:22]([NH:23][C:13]([C@@H:5]([NH:4][C:1]([CH3:2])=[O:3])[CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:15])[CH2:24][CH2:25][CH2:26][N:27]=[C:28]([NH2:30])[NH2:29])=[O:31]
Reactant: CC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: CCOC(=O)[C@@H](N)CCCNC(=N)N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: O=C1CCC(=O)N1O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](Cc1ccccc1)NC(C)=O
Temperature: -15 °C
Reaction time: 5 h

Procedure:
0.829 g (4 mmols) of N-acetyl-L-phenylalanine are dissolved in 40 ml of dimethylformamide. 1.10 g (4 mmols) of finely powdered L-arginine ethyl ester dihydrochloride, 0.56 ml (4 mmols) of triethylamine and 0.69 g (6 mmols) of N-hydroxysuccinimide are added and the mixture is cooled to -15° C. After adding 0.91 g (4.4 mmols) of dicyclohexylcarbodiimide, the mixture is stirred at -5° C. for 7 hours, at 5° C. overnight and at room temperature for 5 hours. The precipitate is filtered off and the solution is concentrated almost to dryness in vacuo on a rotary evaporator. After taking up the residue in 80 ml of water, the pH of the solution is adjusted to 6.0 with triethylamine and the solution is discharged onto a column (1.5×40 cm) of Cm- "Sephadex" (Trade Mark) C-25, equilibrated with 0.05 M triethylammonium acetate of pH 6.0. Elution is carried out with a linear gradient increasing to 0.2 M triethylammonium acetate of pH 6.0 (720 ml; 50 ml/hour; size of fraction: 8 ml). Fractions 75-110, which, according to spotting on filter paper and spraying with Sakaguchi reagent, contains most of the eluted material, is lyophilised. 0.5 ml of ethanol is added to the combined residues and the product is precipitated with 60 ml of ethyl acetate. The precipitate is dried over phosphorus pentoxide in a desiccator.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH2:41])[C:5]2[N:6]=[CH:7][N:8]([C:39]=2[N:40]=1)[C@@H:9]1[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]1[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][OH:49].[H-].[Na+]>>[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][O:49][C:2]1[N:3]=[C:4]([NH2:41])[C:5]2[N:6]=[CH:7][N:8]([C:39]=2[N:40]=1)[C@@H:9]1[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]1[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: OCCc1cccs1
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(N)nc(Cl)nc32)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(N)nc(OCCc4cccs4)nc32)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Temperature: 50 °C

Procedure:
A mixture of 2-chloro-2′,3′,5′-tri-O-(tert-butyldimethylsilyl)adenosine) (Example 1, 1.0 g, 1.5 mmol) and 2-(thiophen-2-yl)ethyl alcohol (5 mL) was heated to 50° C. in a roundbottom flask under a nitrogen atmosphere. Sodium hydride (300 mg, 60% dispersion in mineral oil, 7.7 mmol) was added at a rate so as to control gas evolution. Once complete, the reaction was allowed to cool to room temperature and was carefully quenched with 10 mL of water, then extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with 50 mL of brine, dried over MgSO4, and concentrated to give a brown oil that was purified by chromatography on silica gel eluting with a gradient of 0–10% methanol in CH2Cl2. This afforded 361 mg (33%) of 2-[2-(thiophen-2-yl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)adenosine as an off-white solid which was used without further purification
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][C:3]#[C:4][CH2:5][CH3:6].[H-].[Na+].Cl[C:11]1[C:15]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:14][O:13][N:12]=1.O>O1CCCC1>[CH2:1]([O:7][C:11]1[C:15]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:14][O:13][N:12]=1)[CH2:2][C:3]#[C:4][CH2:5][CH3:6]
Reactant: Clc1nonc1-c1cccnc1
Reactant: CCC#CCCO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCC#CCCOc1nonc1-c1cccnc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-hexyn-1-ol (980 mg, 10 mmol) and sodium hydride (240 mg, 10 mmol) in dry tetrahydrofuran was added a solution of 3-(3-chloro1,2,5-oxadiazol-4-yl)pyridine (450 mg, 2.5 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 2 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(O)C[OH:15]>>[CH:2]([OH:15])([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH3:1]
Reactant: OCCO
Reactant: C=CCCCCCCCCCC
Product: CCCCCCCCCCC(C)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 28.4 %

Procedure:
A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser was charged with 810 g (4.82 mols) of 1-dodecene, 900 g (14.52 mols) of monoethylene glycol, and 100 g of the BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of “VALFOR CP 811 BL-25”). The vapor-phase part of the reaction vessel was displaced with nitrogen and then retained in the atmosphere of nitrogen at normal pressure. The reaction mixture was heated to and kept at 150° C. for three hours and meanwhile kept stirred at 600 rpm to induce reaction. The reaction solution was cooled to room temperature. The dodecene phase in the upper layer was separated and distilled to expel the unaltered dodecene. The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C. to obtain 255 g of a secondary dodecanol ethoxylate composition.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([C:11]3[CH:12]=[C:13]([NH2:17])[CH:14]=[CH:15][CH:16]=3)=[CH:8][C:6]=2[N:7]=1.[CH3:24][O:25][CH2:26][C:27](Cl)=[O:28].C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([C:11]3[CH:12]=[C:13]([NH:17][C:27](=[O:28])[CH2:26][O:25][CH3:24])[CH:14]=[CH:15][CH:16]=3)=[CH:8][C:6]=2[N:7]=1
Reactant: Nc1cccc(-c2cc3nc(Cl)nc(N4CCOCC4)c3s2)c1
Reactant: COCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCC(=O)Nc1cccc(-c2cc3nc(Cl)nc(N4CCOCC4)c3s2)c1

Procedure:
3-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)benzenamine (60 mg), methoxyacetyl chloride (23 mg), and 36 μL of triethylamine in dichloromethane was stirred for 1 h. The reaction mixture was evaporated to give N-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)-2-methoxyacetamide. 70 mg of the crude N-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)phenyl)-2-methoxyacetamide was coupled to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole 7 via General Procedure A. The product was purified by reverse phase HPLC to yield 17.3 mg of 120. MS (Q1) 501 (M)+.
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[CH3:20])=[C:4]([Cl:23])[CH:3]=1.ON1C2C=CC=CC=2N=N1.[Br:34][CH2:35][CH2:36][CH2:37][C:38](O)=[O:39].O>CN(C)C=O.Cl.CN(C)CCCN=C=NCC>[Br:34][CH2:35][CH2:36][CH2:37][C:38]([NH:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[CH3:20])=[C:4]([Cl:23])[CH:3]=1)=[O:39]
Reactant: O=C(O)CCCBr
Reactant: COC(=O)c1ccc2nc(C)n(Cc3ccc(N)cc3Cl)c2n1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1ccc2nc(C)n(Cc3ccc(NC(=O)CCCBr)cc3Cl)c2n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.8 %

Procedure:
Methyl 3-(4-amino-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylate (450 mg) was suspended in N,N-dimethylformamide (5 ml) and 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (391 mg), 1-hydroxybenzotriazole (276 mg) and 4-bromobutanoic acid (318 mg) were added, which was followed by stirring at room temperature for 24 hr. Water (50 ml) was added to the reaction mixture under ice-cooling and the precipitated crystals were collected by filtration and dried under reduced pressure with heating to give methyl 3-(4-((4-bromobutyryl)amino)-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylate (436 mg) as pale-yellow crystals.
Reaction SMILES: [CH3:1][N:2]([CH3:63])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH:9]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]/[CH:53]=[CH:54]\[CH2:55]/[CH:56]=[CH:57]\[CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][C@H:21]([O:27][Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:7].CO.C(Cl)Cl>Cl>[CH3:63][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH:9]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]/[CH:53]=[CH:54]\[CH2:55]/[CH:56]=[CH:57]\[CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][C@H:21]([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:7]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCC(CCCCCCCC/C=C\C[C@@H](CCCCC)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)OC(=O)CCCN(C)C
Agent: Cl
Solvent: CO
Solvent: ClCCl
Product: CCCCC/C=C\C/C=C\CCCCCCCCC(CCCCCCCC/C=C\C[C@H](O)CCCCC)OC(=O)CCCN(C)C
Reaction time: 0.5 h
Yield: 37.1 %

Procedure:
A solution of (6R,8Z,27Z,30Z)-6-(tert-butyldiphenylsilyloxy)hexatriaconta-8,27,30-trien-18-yl 4-(dimethylamino)butanoate (800 mg, 0.95 mmol) in the saturated HCl(g)/MeOH (50 mL) was stirred for 10 minutes. The starting material did not dissolve so anhydrous DCM (12 mL) was added, and the mixture was stirred for 30 minutes. Upon completion, the solution was concentrated in vacuo, saturated sodium bicarbonate (75 mL) was added, and the solution was extracted with ethyl acetate (3×100 mL). The combined ethyl acetate extracts were washed with brine (100 mL), dried on magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography (100% ethyl acetate) to afford the title compound as a colorless oil (0.228 g, 39%). 1H NMR (400 MHz, CDCl3): δ5.61-5.52 (m, 1H), 5.45-5.29 (m, 4H), 4.91-4.83 (m, 1H), 3.66-3.58 (m, 1H), 2.81-235 (m, 2H), 2.75-2.44 (m, 7H), 2.42-2.36 (m, 2H), 2.24-2.18 (m, 2H), 2.10-1.93 (m, 7H), 1.56-1.41 (m, 6H), 1.40-1.20 (m, 36H), 0.93-0.85 (m, 6H).
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=3)[O:16][C:15](=[O:25])[CH:14]=2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]1([CH2:32][O:33][CH2:34][CH2:35][CH2:36][Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2([CH2:36][CH2:35][CH2:34][O:33][CH2:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:22]3[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=3)[O:16][C:15](=[O:25])[CH2:14]2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc2c(-c3cn(Cc4ccccc4)cn3)cc(=O)oc2c1
Reactant: Br[Mg]CCCOCc1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc2c(c1)OC(=O)CC2(CCCOCc1ccccc1)c1cn(Cc2ccccc2)cn1
Reaction time: 1 h

Procedure:
A solution of 1 mmol of 4-(1-benzyl-1H-imidazol-4-yl)-7-methoxychromen-2-one in 5 ml of tetrahydrofuran is added to a solution of 3 mmol of 3-(phenylmethoxy)propylmagnesium bromide [183312-54-1] in 5 ml of tetrahydrofuran. The mixture is subsequently stirred for 1 hour and then poured into saturated aqueous ammonium chloride solution. It is extracted with diethyl ether (3×). The combined organic phases are dried over sodium sulphate and evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60F) on the basis of the Rf value.
Reaction SMILES: [CH:1]1([CH3:12])[CH2:6][CH2:5][CH:4]([C:7]([OH:10])([CH3:9])[CH3:8])[CH:3]([OH:11])[CH2:2]1.N1C=CC=CC=1.[C:19](Cl)(=[O:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]/[CH:27]=[CH:28]\[CH2:29]/[CH:30]=[CH:31]\[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]>C(Cl)Cl>[C:19]([OH:37])(=[O:10])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]/[CH:27]=[CH:28]\[CH2:29]/[CH:30]=[CH:31]\[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].[CH:1]1([CH3:12])[CH2:6][CH2:5][CH:4]([C:7]([OH:10])([CH3:9])[CH3:8])[CH:3]([OH:11])[CH2:2]1
Reactant: CCCCC/C=C\C/C=C\CCCCCCCC(=O)Cl
Agent: CC1CCC(C(C)(C)O)C(O)C1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCC/C=C\C/C=C\CCCCCCCC(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 250 mL one necked bottomed flask, was charged with 7.0 g (0.040 moles) of 3,8-p-menthanediol, 100 mL of anhydrous methylene chloride and 6.9 g (0.87 moles) of anhydrous pyridine. 25.5 g (0.085 moles) of Linoleoyl chloride was pre-dissolved in 25-30 mL of anhydrous methylene chloride and charged into the additional funnel. The acid chloride solution was then added dropwise to the solution at room temperature under a nitrogen blanket over a period of 30 minutes. Upon completion of the addition, the reaction was stirred for two hours before the addition funnel was replaced with a reflux condenser. The reaction was then heated to reflux for two additional hours before cooling to ambient temperature and stirring overnight.
Reaction SMILES: C(O[C:4]([CH3:13])=[CH:5][C:6](=O)[C:7]([O:9][CH2:10][CH3:11])=[O:8])C.[C:14]([CH2:16][C:17]([NH2:19])=[O:18])#[N:15].C(=O)([O-])[O-].[K+].[K+].Cl>CC(C)=O>[C:14]([C:16]1[C:17](=[O:18])[NH:19][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][C:4]=1[CH3:13])#[N:15]
Reactant: CCOC(=O)C(=O)C=C(C)OCC
Reactant: N#CCC(N)=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)c1cc(C)c(C#N)c(=O)[nH]1
Temperature: 85 °C
Reaction time: 0.5 h
Yield: 65.8 %

Procedure:
To a stirred solution of ethyl 4-ethoxy-2-oxopent-3-enoate (22.5 g, 121 mmol) and 2-cyanoacetamide (9.0 g, 107 mmol) in acetone (250 mL) was added potassium carbonate (15.8 g, 114 mmol). The reaction was refluxed (85° C. oil bath) for 10 hr (the reaction formed a thick ppt. in a deep red solution). The slurry was added to cold 1 N HCl (230 mL) in ice. After stirring for 30 min. the suspension was filtered, washed with water and dried under vacuum to give the product ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate (14.51 g, 70.4 mmol, 65.7% yield) as a light pink solid.
Reaction SMILES: [CH3:1][O:2][C:3]([O:8][CH3:9])([CH3:7])[C:4](=[O:6])[CH3:5].CO[CH:12](OC)[N:13]([CH3:15])[CH3:14]>>[CH3:12][N:13]([CH3:15])[CH:14]=[CH:5][C:4](=[O:6])[C:3]([O:8][CH3:9])([O:2][CH3:1])[CH3:7]
Reactant: COC(C)(OC)C(C)=O
Reactant: COC(OC)N(C)C
Product: COC(C)(OC)C(=O)C=CN(C)C
Temperature: 100 °C
Reaction time: 42 h
Yield: 99.5 %

Procedure:
A mixture of 100 g of 3,3-dimethoxy-2-butanone and 99.2 g of N,N-dimethylformamide dimethylacetal was stirred at 100° C. for 42 hours. After cooling the reaction mixture, the mixture was concentrated under reduced pressure to give 141 g of 1-dimethylamino-4,4-dimethoxy-1-penten-3-one.