Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[S:10](=[O:11])[CH2:9][CH2:8][CH2:7][S:6]1=[O:12].[CH3:23][NH:24][CH2:25][CH2:26][C:27]1[CH:36]=[CH:35][C:32]([O:33][CH3:34])=[C:29]([O:30][CH3:31])[CH:28]=1.CS(C)=O>O>[ClH:1].[CH3:31][O:30][C:29]1[CH:28]=[C:27]([CH:36]=[CH:35][C:32]=1[O:33][CH3:34])[CH2:26][CH2:25][N:24]([CH3:23])[CH2:2][CH2:3][CH2:4][C:5]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[S:10](=[O:11])[CH2:9][CH2:8][CH2:7][S:6]1=[O:12]
Reactant: COc1ccc(C2(CCCCl)S(=O)CCCS2=O)cc1OC
Reactant: CNCCc1ccc(OC)c(OC)c1
Solvent: CS(C)=O
Solvent: O
Product: COc1ccc(CCN(C)CCCC2(c3ccc(OC)c(OC)c3)S(=O)CCCS2=O)cc1OC
Product: Cl

Procedure:
3.65 g of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,3-dioxide, 7.8 g of N-methyl-homoveratrylamine and 20 ml of dimethyl sulphoxide are heated at 50° C. under argon for 16 hours. The solution is then poured into 200 ml of water and made strongly alkaline. The excess N-methyl-homoveratrylamine is extracted with ether. The alkaline solution is then extracted with methylene chloride. The methylene chloride extracts are dried over magnesium sulphate. After evaporation of the solvent, the residue is taken up in acetone and treated with hydrogen chloride in dioxane (up to pH 2). The crystalline residue is recrystallized from acetone/acetonitrile and there is obtained N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine-1,3-dioxide hydrochloride of melting point 148°-149° C. (diastereomeric mixture).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[N:5][N:4]=[N:3]1.C([Mg]Cl)(C)C.CON(C)[C:15](=[O:25])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][O:23][CH3:24])[CH:17]=1.Cl>C1COCC1>[CH3:24][O:23][CH2:22][C:18]1[CH:17]=[C:16]([C:15]([C:6]2[N:2]([CH3:1])[N:3]=[N:4][N:5]=2)=[O:25])[CH:21]=[CH:20][CH:19]=1
Reactant: COCc1cccc(C(=O)N(C)OC)c1
Reactant: Cn1cnnn1
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: C1CCOC1
Product: COCc1cccc(C(=O)c2nnnn2C)c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 33 %

Procedure:
To a stirred solution of 1-methyl-1H-tetrazole (9.35 g, 111 mmol) in anhydrous THF (360 mL), cooled to 0° C. with a brine/ice bath, was added dropwise a solution of isopropylmagnesium chloride (2 M in THF, 55.6 mL, 111 mmol). After the addition was over, the resulting cloudy suspension was stirred for 15 min at 0° C. A solution of N-methoxy-3-(methoxymethyl)-N-methylbenzamide (19.4 g, 92.6 mmol) in THF (60 mL) was then added dropwise while keeping the internal temperature below 5° C. The reaction mixture was then allowed to warm up and stirred at room temperature for 24 h. The reaction mixture was poured into a mixture of ice-cold water (150 mL) and aq. HCl (1 M, 150 mL), the layers were separated, the water phase was extracted with ethyl acetate (2×150 mL) and the combined organic layers were dried (MgSO4). Purification on silica gel afforded [3-(methoxymethyl)phenyl](1-methyl-1H-tetrazol-5-yl)methanone as an oil [7.17 g, yield 33%; HPLC/MS m/z=233 (M+H); log P(HCOOH)=2.01].
Reaction SMILES: [C:1]([CH2:3][N:4]([C:12]1[N:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:15]=[CH:14][CH:13]=1)C(=O)OC(C)(C)C)#[N:2].C(O)(C(F)(F)F)=O>ClCCl>[C:17]1([N:16]2[C:12]([NH:4][CH2:3][C:1]#[N:2])=[CH:13][CH:14]=[N:15]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(C)(C)OC(=O)N(CC#N)c1ccnn1-c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#CCNc1ccnn1-c1ccccc1
Reaction time: 5 h
Yield: 65.3 %

Procedure:
To a solution of tert-butyl (cyanomethyl)(1-phenyl-1H-pyrazol-5-yl)carbamate (4.38 g) in dichloromethane was added TFA (16.7 g) at room temperature, and the mixture was stirred for 5 hr. The reaction mixture was concentrated under reduced pressure, and adjusted to pH 9-10 with 1N aqueous sodium hydroxide solution. The reaction mixture was extracted with dichloromethane. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane/methanol) to give the title compound (1.90 g).
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:16][C:17]([O:19]C)=[O:18].[CH2:21](N(CC)CC)C.CN(C)C=O>O>[CH3:21][N:8]([CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:16][C:17]([OH:19])=[O:18]
Reactant: COC(=O)CCl
Reactant: CCN(CC)CC
Reactant: NC(c1ccccc1)c1ccccn1
Solvent: CN(C)C=O
Solvent: O
Product: CN(CC(=O)O)C(c1ccccc1)c1ccccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.8 %

Procedure:
A mixture of 44 parts of α-phenyl-2-pyridinemethanamine, 27 parts of methyl chloroacetate, 30 parts of N,N-diethylethanamine and 270 parts of N,N-dimethylformamide was stirred overnight at room temperature. The reaction mixture was poured into 1000 parts of water. The product was extracted with 1,1'-oxybisethane. The extract was washed three times with water, dried, filtered and evaporated, yielding 37 parts (62.8%) of methyl N-[phenyl(2-pyridinyl)methyl]glycine as a residue.
Reaction SMILES: [Br:1][C:2]1[C:3]([C@@H:19]([NH:29][S@](C(C)(C)C)=O)[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)=[N:4][CH:5]=[C:6]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[CH:7]=1.[ClH:36].O1CCOCC1>CO>[ClH:36].[NH2:29][C@H:19]([C:3]1[N:4]=[CH:5][C:6]([N:8]2[C:9](=[O:18])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:16]2=[O:17])=[CH:7][C:2]=1[Br:1])[CH2:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=1
Reactant: CC(C)(C)[S@](=O)N[C@@H](Cc1cc(F)cc(F)c1)c1ncc(N2C(=O)c3ccccc3C2=O)cc1Br
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: N[C@@H](Cc1cc(F)cc(F)c1)c1ncc(N2C(=O)c3ccccc3C2=O)cc1Br
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
(S)—N—((S)-1-(3-bromo-5-(1,3-dioxoisoindolin-2-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (30D, 2.6 G, 4.6 mmol) was dissolved in 40 mL of methanol and cooled to 0° C. To it was added 4N HCl/1,4-dioxane (4.6 ml). The reaction mixture was allowed to stir at room temperature for 10 minutes and concentrated to afford product (S)-2-(6-(1-amino-2-(3,5-difluorophenyl)ethyl)-5-bromopyridin-3-yl)isoindoline-1,3-dione hydrochloride. To the mixture of the above HCl salt (˜4.6 mmol) and di-tert-butyl dicarbonate (1 g, 4.6 mmol) in 50 mL of CH2Cl2 was added triethylamine (1.28 mL, 9.2 mmol) at 0° C. The reaction mixture was stirred for overnight and concentrated in vacuo. The residue was partitioned between EtOAc and H2O. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Then it was purified on silica gel chromatography eluting with EtOAc/hexanes to yield the title compound. MS (m/z) 559.71 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([N:14]=[CH:15][C:16]=3[C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)[CH:13]=2)=[CH:4][CH:3]=1.CCN(CC)CC.[CH2:31]([N:33]=[C:34]=[O:35])[CH3:32]>COCCOC>[CH2:31]([NH:33][C:34]([NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:16]2[CH:15]=[N:14][N:12]3[CH:13]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH:9]=[CH:10][C:11]=23)[CH:18]=1)=[O:35])[CH3:32]
Reactant: Nc1cccc(-c2cnn3cc(-c4ccc(F)cc4)ccc23)c1
Reactant: CCN=C=O
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: CCNC(=O)Nc1cccc(-c2cnn3cc(-c4ccc(F)cc4)ccc23)c1
Temperature: 60 °C
Yield: 91.8 %

Procedure:
A solution of 3-[6-(4-fluoro-phenyl)-pyrazolo[1,5-a]pyridin-3-yl]-phenylamine (Example 118, 50 mg, 0.16 mmol), Et3N (45 μL, 0.32 mmol) and ethyl isocyanate (26 μL, 0.32 mmol) in dry DME (2 ml) was stirred and heated at 60° C. under N2 for 24 hours [Further ethyl isocyanate (30 μL) was added after 7 hours]. The reaction mixture was evaporated and dried under vacuum to give the title compound (55 mg, solid). 1H NMR (400 MHz, DMSO-d6): 9.09 (1H, s), 8.53 (1H, s), 8.36 (1H, s), 8.02 (1H, d), 7.93-7.83 (3H, m), 7.72 (1H, dd), 7.38-7.29 (3H, m), 7.27-7.22 (2H, m), 6.15 (1H, t), 3.19-3.09 (2H, m), 1.08 (3H, t).
Reaction SMILES: [CH:1]1([CH:6]2[O:10][B:9]([OH:11])[C:8]3[CH:12]=[C:13]([NH:16][C:17](=[O:28])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4C(F)(F)F)[CH:14]=[CH:15][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:29]C1C=CC=CC=1C(Cl)=O>>[CH:1]1([CH:6]2[O:10][B:9]([OH:11])[C:8]3[CH:12]=[C:13]([NH:16][C:17](=[O:28])[C:18]4[CH:23]=[CH:22][C:21]([F:29])=[CH:20][CH:19]=4)[CH:14]=[CH:15][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(Cl)c1ccccc1F
Reactant: O=C(Nc1ccc2c(c1)B(O)OC2C1CCCC1)c1ccccc1C(F)(F)F
Product: O=C(Nc1ccc2c(c1)B(O)OC2C1CCCC1)c1ccc(F)cc1

Procedure:
The title compound was prepared using a procedure similar to that of N-(3-cyclopentyl-1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-2-trifluoromethyl-benzamide with 2-fluorobenzoyl chloride replacing 2-trifluoromethylbenzoyl chloride. Data: LCMS (M/Z): 340 (M+H); 1H NMR (acetone) δ: 9.54 (br. s., 1H), 8.17 (d, J=2.0 Hz, 1H), 8.03-8.11 (m, 3H), 7.80 (dd, J=8.3, 2.1 Hz, 1H), 7.37 (d, J=8.2 Hz, 1H), 7.22-7.30 (m, 2H), 5.12 (d, J=4.8 Hz, 1H), 2.26-2.35 (m, 1H), 1.81-1.91 (m, 1H), 1.62-1.73 (m, 2H), 1.49-1.57 (m, 2H), 1.40-1.49 (m, 1H), 1.30-1.39 (m, 1H), 1.09-1.20 (m, 1H).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([O:19][CH2:20][CH2:21][NH2:22])[CH3:18]>>[CH2:17]([O:19][CH2:20][CH2:21][NH:22][C:8](=[O:9])[CH:7]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:18]
Reactant: CCOCCN
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Product: CCOCCNC(=O)C(c1ccccc1)c1ccccc1

Procedure:
The title compound, white solid, m.p. 83.5-86.2° C. and MS: m/e=283 (M+H+) was prepared in accordance with the general method of example 1 from diphenylacetyl chloride and 2-ethoxy-ethylamine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[CH2:9][NH:8][CH2:7][CH2:6]2.[C:16](Cl)(=[O:19])[CH:17]=[CH2:18].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1.O>[C:16]([N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][C:12]([N+:13]([O-:15])=[O:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:9]1)(=[O:19])[CH:17]=[CH2:18]
Reactant: C=CC(=O)Cl
Reactant: COc1cc2c(cc1[N+](=O)[O-])CNCC2
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CC(=O)N1CCc2cc(OC)c([N+](=O)[O-])cc2C1
Reaction time: 16 h
Yield: 84.2 %

Procedure:
A solution of 6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (1.6 g, 7.7 mmol) in dichloromethane (30 mL) was treated with acryloyl chloride (1.9 mL, 23 mmol, TCl), triethylamine (3.2 mL, 23 mmol, Aldrich), and catalytic 4-dimethylaminopyridine (50 mg 0.41 mmol, Aldrich). The mixture was stirred for 16 h, diluted with excess water, and extracted with ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated to provide 2-acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (1.7 g, 84%). 1H NMR (400 MHz, DMSO-d6) is complicated due to amide rotomers δ ppm 2.86-2.95 (two triplets at 2.88 and 2.93, 2 H), 3.72-3.82 (two triplets at 3.74 and 3.80, 2 H), 3.89 (m, 3 H), 4.63-4.80 (two singlets at 4.65 and 4.77, 2 H), 5.73 (app d, J=10.3 Hz, 1 H), 6.16 (dd, J=16.7, 2.4 Hz, 1 H), 6.89 (dd, J=16.9, 10.3 Hz, 1 H), 7.21 (s, 1 H), 7.78-7.84 (two singlets at 7.79 and 7.83, 1 H); ESIMS (M+H)+=263.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[BrH:21].BrBr>C(O)(=O)C>[Br:21][CH:9]([C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:17])=[O:18])=[CH:12][CH:11]=1)[C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[O:20]
Reactant: Br
Reactant: CS(=O)(=O)c1ccc(CC(=O)c2ccc(F)cc2)cc1
Agent: BrBr
Solvent: CC(=O)O
Product: CS(=O)(=O)c1ccc(C(Br)C(=O)c2ccc(F)cc2)cc1
Reaction time: 1 h
Yield: 95 %

Procedure:
To a stirred slurry of 1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl) ethanone from Step 1 (3.03 g, 10.38 mmol) in acetic acid (40 mL) was added HBr in acetic acid (2 mL, 48% by wt. ) and bromine (0.64 mL, 1.99 g, 12.45 mmol). Within minutes the slurry became homogeneous. After 1 hour, the reaction was concentrated in vacuo, diluted with methylene chloride and reconcentrated in vacuo yielding 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl) ethanone as a tan solid (3.53 g, 95%) which could be used without further purification. mp 140°-141° C., 1H NMR (CDCl3) 300 mHz δ8.05 (dd, J=5.16, 8.84 Hz, 2H), 7.96 (d, J=8.48 Hz, 2H), 7.75 (d, J=8.48 Hz, 2H), 7.17 (t, J=8.48 Hz, 2H), 6.29 (s, 1H), 3.06 (s, 3H). MS: m/e 371/373 (MH+). HRMS Δ=5.5 mmu.
Reaction SMILES: BrC1C=NN(CC2C=C(C=CC=2)C(OC)=O)C=1.BrC1C=NNC=1.[NH:24]1[CH:28]=[C:27]([C:29]2[CH:38]=[CH:37][CH:36]=[C:35]3[C:30]=2[CH2:31][CH2:32][CH2:33][N:34]3[C:39](=[O:52])[CH2:40][CH2:41][CH2:42][O:43][C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([CH3:50])[C:45]=2[CH3:51])[CH:26]=[N:25]1.BrCC1C=C(C=CC=1)C(OC)=O.[Br:65][C:66]1[CH:71]=[CH:70][CH:69]=[C:68]([CH2:72]Br)[CH:67]=1>>[Br:65][C:66]1[CH:67]=[C:68]([CH:69]=[CH:70][CH:71]=1)[CH2:72][N:24]1[CH:28]=[C:27]([C:29]2[CH:38]=[CH:37][CH:36]=[C:35]3[C:30]=2[CH2:31][CH2:32][CH2:33][N:34]3[C:39](=[O:52])[CH2:40][CH2:41][CH2:42][O:43][C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([CH3:50])[C:45]=2[CH3:51])[CH:26]=[N:25]1
Reactant: Cc1cccc(OCCCC(=O)N2CCCc3c(-c4cn[nH]c4)cccc32)c1C
Reactant: BrCc1cccc(Br)c1
Agent: Brc1cn[nH]c1
Agent: COC(=O)c1cccc(CBr)c1
Agent: COC(=O)c1cccc(Cn2cc(Br)cn2)c1
Product: Cc1cccc(OCCCC(=O)N2CCCc3c(-c4cnn(Cc5cccc(Br)c5)c4)cccc32)c1C

Procedure:
The title compound was prepared using a procedure analogous to methyl 3-((4-bromo-1H-pyrazol-1-yl)methyl)benzoate except that 4-bromo-1H-pyrazole was replaced with 1-(5-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-one and methyl 3-(bromomethyl)benzoate was replaced with 1-bromo-3-(bromomethyl)benzene. LCMS, [M+H]+=560.2.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[C:5]([NH2:14])=[CH:4][N:3]=1.CN([CH:18]=[O:19])C.C(N1C=CN=C1)(N1C=CN=C1)=O>CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]2[C:5]([NH:14][C:18](=[O:19])[N:8]2[CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])=[CH:4][N:3]=1
Reactant: CN(C)C=O
Reactant: CCC(CC)Nc1nc(Cl)ncc1N
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Product: CCC(CC)n1c(=O)[nH]c2cnc(Cl)nc21
Temperature: 100 °C

Procedure:
To a microwave vial is added the crude (2-chloro-5-amino-pyrimidin-4-yl)-(1-ethyl-propyl)-amine (0.5 g, 2.3 mmol) and anhydrous DMF (15 mL) followed by 1,1′-carbonyldiimidazole (1.1 g, 7.0 mmol). Sealed vial and microwave are heated at 100° C. for 10 min. The reaction mixture is diluted with EtOAc, washed with water, dried over Na2SO4, and concentrated in vacuo. Purification with column chromatography (SiO2, EtOAC/Hexane 1:1) gives 0.3 g of 2-chloro-9-(1-ethyl-propyl)-7,9-dihydro-purin-8-one. LCMS: 241.1 (M+H)+
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH3:4].[CH3:5][C:6]1[N+](CC2C(N)=NC(C)=NC=2)=CS[C:7]=1[CH2:20][CH2:21]OP(O)(O)=O.[CH:27](O)([CH3:29])[CH3:28]>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:27][CH2:21][CH2:20][CH2:7][CH2:6][CH3:5].[CH3:1][CH2:2][CH:3]=[CH:4][CH2:28][CH2:27][CH2:29][CH2:21][CH2:20][CH2:7][CH2:6][CH3:5]
Reactant: Cc1ncc(C[n+]2csc(CCOP(=O)(O)O)c2C)c(N)n1
Reactant: CC(C)O
Reactant: C=CCC
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Product: C=CCCCCCCCC
Product: CCC=CCCCCCCCC
Temperature: 60 °C
Reaction time: 4 h

Procedure:
Estolides prepared according to the method set forth in Example 1 (20 mol) and a second-generation Grubbs' catalyst (e.g., C827, 25 ppm) are added to a Parr Reactor and degassed with argon for 1 hr. 1-Butene is added while heating to 60° C. while keeping the pressure of the reaction between about 25 to about 60 psi. The 1-butene is added using a one-way check valve to prevent backflow into the 1-butene cylinder. After 4 hrs, the pressure is released and vented into the fume hood. After allowing the reactor to cool to room temperature, a 50 ml 1M tris-hydroxymethylphopshine (THMP) solution in isopropanol (IPA) (50 mol equiv.) is added, and the reactor is degassed with argon and heated to 60° C. for 18 hrs. The reactor is then again allowed to cool to room temperature. The crude reaction product is then washed with water and brine. The washed reaction product is them dried over sodium sulfate, filtered, and distilled to provide 1-decene, 3-dodecene, estolides having a C10 cap with a terminal double bond, and estolides having a C12 cap with an internal double bond.
Reaction SMILES: [C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[CH:2].[Li][CH2:17][CH2:18][CH2:19][CH3:20].B(F)(F)F.[NH4+].[Cl-].[OH2:27]>C1COCC1>[CH2:17]([O:27][CH2:13][C@H:12]([OH:11])[CH2:14][C:2]#[C:1][CH:3]1[CH2:4][CH2:5][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][CH2:8]1)[C:18]1[CH:3]=[CH:1][CH:2]=[CH:20][CH:19]=1
Reactant: C#CC1CCN(C(=O)OC(C)(C)C)CC1
Reactant: O
Reactant: [Li]CCCC
Agent: FB(F)F
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(C#CC[C@@H](O)COCc2ccccc2)CC1
Temperature: -78 °C

Procedure:
Commercially available tert-butyl 4-ethynylpiperidine-1-carboxylate was dissolved in 40 ml of THF and cooled to −78° C. forming a white slurry. Titrated n-BuLi (2.2 M in hexanes, 23.9 ml, 52.6 mmol) was added drop wise with stirring. The clear colorless solution was stirred at −78° C. for 5 minutes. A solution of the R-(+) benzyl glycidyl epoxide (8.63 g, 52.6 mmol) in THF (20 ml) was added drop wise. BF3 etherate (8.43 g, 59.7 mmol) was then added drop wise with a syringe and the solution stirred at −78° C. for 1 hour. Saturated aqueous NH4Cl was added (100 ml), the mixture warmed to RT, diluted with water to dissolve any remaining solids, and extracted with iPrOAc (3×100 ml). The organic fractions were combined, washed with brine, dried over MgSO4, filtered and stripped. Crude product was purified by chromatography on SiO2 eluting with 30% EtOAc:Hexanes. The alcohol was repurified by chromatography on a C18 reversed phase column (12-100% water:acetonitrile 0.1% TFA as two runs.). Product containing fractions were combined, reduced in volume by approximately 50%, made basic by addition of saturated aqueous NaHCO3, water was added to dissolve some white solids, and the mixture extracted with iPrOAc (3×100). The organic fractions were combined, washed with brine, dried over MgSO4, filtered, and stripped to give the titled compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:18][NH:19][O:20][CH3:21].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CCOCC>[CH3:21][O:20][N:19]([CH3:18])[C:14]([CH:10]1[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:16]
Reactant: CNOC
Reactant: CC(C)(C)OC(=O)N1CCOC(C(=O)O)C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOCC
Solvent: ClCCl
Product: CON(C)C(=O)C1CN(C(=O)OC(C)(C)C)CCO1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of (±)-4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (1.51 g, 6.53 mmol), N,O-dimethylhydroxylamine hydrochloride (0.83 g, 8.49 mmol) and i-Pr2NEt (3.1 mL, 17.6 mmol) in CH2Cl2 (30 mL) was added solid HATU (3.01 g, 7.85 mmol). The mixture was stirred at rt for 3 d, diluted with ether (175 mL), washed with 5% aq HCl (2×50 mL) and satd aq NaHCO3 (50 mL) and dried over MgSO4. Removal of the solvent left (±)-tert-butyl 2-(methoxy(methyl)carbamoyl)morpholine-4-carboxylate (1.73 g, 96%) as an oil.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:9]1(C)[C:10]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=1.N1C=CC=C[CH:21]=1.C>C(OCC)C>[C:13]1([CH3:21])[CH:14]=[CH:9][C:10]([S:15]([CH2:2][CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6])(=[O:16])=[O:17])=[CH:11][CH:12]=1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: c1ccncc1
Reactant: COC(=O)CCCO
Solvent: CCOCC
Product: COC(=O)CCCS(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C

Procedure:
25 g. Methyl 4-hydroxybutanoate were mixed with 47.5 g. toluene-sulphonyl chloride and 250 ml. dry pyridine at 5° C. and kept at this temperature for 17 hours, whereafter the reaction mixture was poured into 2 liters ice water. The oil thus formed was extracted with diethyl ether and the ethereal extract was washed with 500 ml. 6 N hydrochloric acid to remove excess pyridine, followed by washing with a saturated aqueous solution of sodium bicarbonate until neutral. Concentration of the organic layer gave 32.5 g. of a yellow oil which was dissolved in diethyl ether, treated with decolorising charcoal, filtered and the filtrate concentrated to give 30.5 g. of a pale yellow oil which slowly crystallised at 5° C. Thin layer chromatography (petroleum ether/dichloromethane/acetone 6:3:1 v/v/v) showed the product to be pure. The methyl 4-(p-toluene-sulphonyl)-butanoate thus obtained had a melting point of 23° C.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5](=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12]P(OCC)(OCC)=O.C1OCCOCCOCCOCCOC1.[CH3:37][N:38]1[CH2:43][CH2:42][C:41](=O)[CH2:40][CH2:39]1>C1COCC1>[CH3:3][O:4][C:5](=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=[C:41]1[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]1
Reactant: CN1CCC(=O)CC1
Reactant: CCOP(=O)(Cc1ccccc1C(=O)OC)OCC
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccccc1C=C1CCN(C)CC1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 21.2 %

Procedure:
NaH (55-65%, 231 mg; 5.3 mmol; 1.2 eq.) was added to a cold (0° C.) solution of 2-(diethoxy-phosphorylmethyl)-benzoic acid methyl ester (from Intermediate B11 step 1) (1.52 g; 5.3 mmol; 1.2 eq.) and 15-crown-5 (26 μL; 0.13 mmol; 0.03 eq.) in THF (5 mL) and the reaction mixture was stirred at room temperature for 30 minutes whereupon a solution of 1-methyl-piperidin-4-one (500 mg; 4.42 mmol; 1 eq.) in THF (5 mL) was added dropwise over 10 minutes at 0° C. The resulting mixture was stirred at room temperature for 3.5 hours then concentrated in vacuo. The residue was taken up in water and extracted with EA (2×). The combined organics were washed with 1M NaOH then brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM to 10% MeOH in DCM) afforded the title compound (230 mg, 21%) as a yellow oil. UPLC/MS: (MS+) 246.3 ([M+H]+).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]2[O:13][CH:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1>O.C(Cl)Cl>[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C@@H:11]2[CH2:12][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:9][C@H:10]2[OH:13])=[CH:18][CH:17]=1
Reactant: c1ccc(CN2CC3OC3C2)cc1
Reactant: COc1ccc(O)cc1
Solvent: ClCCl
Solvent: O
Product: COc1ccc(O[C@@H]2CN(Cc3ccccc3)C[C@H]2O)cc1

Procedure:
A mixture of 17.5 g. (0.10 mole) of 1-benzyl-3,4-epoxypyrrolidine, 13.4 g. (0.11 mole) of p-methoxyphenol, and 3 drops of water was heated on a steam bath overnight. The dark residue was dissolved in methylene chloride and the solution was washed with two 50-ml. portions of 5% sodium hydroxide. The methylene chloride layer was dried over anhydrous sodium sulfate and concentrated to give 23.7 g. of viscous dark oil. This oil was chromatographed on 480 g. of silica gel 60 and the product was eluted with a 1:1 benzene:ether solution. The appropriate fractions were concentrated to give 10.0 g. of a yellow oil which crystallized upon scratching. The solid was recrystallized from cyclohexane to yield 7.2 g. (24%) tan solid, m.p. 84°-5° C.