Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][C:10]([OH:12])=O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:15][O:16][C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([NH2:24])[CH:19]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:15][O:16][C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:10](=[O:12])[CH2:9][O:8][C:7]2[CH:6]=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[CH:14][CH:13]=2)[CH:19]=1
Reactant: CC(=O)c1ccc(OCC(=O)O)cc1
Reactant: COC(=O)c1cccc(N)c1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cccc(NC(=O)COc2ccc(C(C)=O)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.5 %

Procedure:
To a solution of the 4-acetylphenoxy acetic acid (97 mg, 0.5 mmol) and 3-amino benzoic acid methyl ester (113 mg, 0.75 mmol) in DMF (5.0 mL) were added EDCHCl (144 mg, 0.75 mmol), HOBT (101 mg, 0.75 mmol), and DIPEA (0.13 mL, 0.75 mmol). The reaction mixture was stirred at room temperature overnight, and then partitioned between Ethyl acetate and brine. The organic phase was dried (anhydrous MgSO4), and concentrated. Purification by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=6:3:1) gave 3-[2-(4-acetyl-phenoxy)acetylamino]-benzoic acid methyl ester as a white solid (158 mg, 97% yield).
Reaction SMILES: [C@H:1]1([NH:10][C:11]2[C:12]3[CH:19]=[CH:18][N:17]([C@H:20]4[CH2:24][C@H:23]([OH:25])[C@H:22]([CH2:26][OH:27])[CH2:21]4)[C:13]=3[N:14]=[CH:15][N:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.Cl[S:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])(=[O:46])=[O:45]>C(C#N)(C)=O>[C:50]([O:49][C:48](=[O:54])[NH:47][S:44]([O:27][CH2:26][C@@H:22]1[CH2:21][C@@H:20]([N:17]2[C:13]3[N:14]=[CH:15][N:16]=[C:11]([NH:10][C@H:1]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH2:3][CH2:2]4)[C:12]=3[CH:19]=[CH:18]2)[CH2:24][C@@H:23]1[OH:25])(=[O:46])=[O:45])([CH3:53])([CH3:51])[CH3:52]
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)Cl
Reactant: OC[C@@H]1C[C@@H](n2ccc3c(N[C@@H]4CCc5ccccc54)ncnc32)C[C@@H]1O
Agent: CC(=O)C#N
Agent: Cc1cc(C(C)(C)C)nc(C(C)(C)C)c1
Product: CC(C)(C)OC(=O)NS(=O)(=O)OC[C@@H]1C[C@@H](n2ccc3c(N[C@@H]4CCc5ccccc54)ncnc32)C[C@@H]1O
Temperature: 25 °C
Yield: 37 %

Procedure:
(1S,2S,4R)-4-{4-[(1R)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]-pyrimidin-7-yl}-2-(hydroxymethyl)cyclopentanol (27.6 mg, 0.117 mmol) and 2,6-di-tert-butyl-4-methylpyridine (48.5 mg, 0.236 mmol) were suspended in AcCN (1.57 mL) and cooled to 0° C. tert-Butyl (chlorosulfonyl)carbamate was added and the mixture was allowed to warm to rt overnight. The reaction was quenched via addition of MeOH (1.00 mL) and concentrated in vacuo. Silica gel chromatography eluting with a gradient of 0 to 10% MeOH in DCM afforded the title compound (15.2 mg, 37%). LC/MS: Rt=1.29 min, ES+ 544 (FA standard).
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][C:8](I)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14]>[Cu]I>[I:1][C:2]1[CH:10]=[CH:9][C:8]([C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: C#C[Si](C)(C)C
Reactant: O=C(O)c1cc(I)ccc1I
Agent: [Cu]I
Product: C[Si](C)(C)C#Cc1ccc(I)c(C(=O)O)c1
Reaction time: 16 h
Yield: 73 %

Procedure:
1.12 g of 2,5-diiodobenzoic acid (3 mmol, 1 eq.), 210 mg of dichlorobis-triphenylphosphinepalladium(II) (0.3 mmol, 0.1 eq.) and 200 mg of copper(I) iodide (1 mmol, 0.34 eq.) are dissolved in 60 ml of a THF/TEA mixture (3/1). After the addition of 425 μl of trimethylsilylacetylene (3 mmol, 1 eq.), stirring is continued at room temperature for 16 hours in the dark. The reaction medium is then evaporated to dryness and the residue obtained is purified by flash chromatography on silica 60H (hexane/EtOAc/AcOH: 70/30/1%) to give 754 mg of 2-iodo-5-trimethylsilylethynylbenzoic acid in the form of fine yellow needles after drying under vacuum (yield: 73%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[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.CN(C=O)C>[F:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[C:13]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:18][CH:19]=1)=[O:29]
Reactant: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(OS(=O)(=O)C(F)(F)F)ccc2c1
Reactant: OB(O)c1c(F)cccc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(-c3c(F)cccc3F)ccc2c1

Procedure:
Charge a flask with trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (2.0 g, 3.7 mmol), 2,6-difluorophenyl boronic acid (1.17 g, 7.4 mmol), tetrakis(triphenylphosphine)palladium (0) (855 mg, 0.74 mmol) and potassium phosphate (4.7 g, 22.2 mmol) add 100 mL, of dry DMF and heat under nitrogen at 100° C. for two hours. Cool the reaction and filter. Purify on an SCX column eluting with 2N ammonia/methanol. Purify further on a silica gel column eluting with a gradient of 0-10% methanol/methylene chloride. The yield is 1.5 g (81%): 1H-NMR (CDCl3, 400 MHz) δ 7.90 (d, J=8.4 Hz, 1H); 7.63 (d, J=8.4 Hz, 1H); 7.62 (d, J=9.2 Hz, 2H); 7.39 (d, J=8.4 Hz, 1H); 7.23 (d, J=2.8 Hz, 1H); 7.18-7.08 (m, 2H); 6.78 (d, J=10.4 Hz, 2H); 6.74 (s, 2H); 4.11-4.08 (m, 2H); 3.95 (s, 3H); 2.75 (t, J=6.4 Hz, 2H); 2.49-2.49 (m, 4H); 1.63-1.58 (m, 4H); 1.47-1.44 (m, 2H).
Reaction SMILES: C(OC(=O)C)(=[O:3])C.[CH2:8]([N:10]([CH2:13][CH3:14])[CH2:11][CH3:12])C.[C:15]([O:19][C:20]([CH2:22][NH:23]CCNC)=[O:21])([CH3:18])([CH3:17])[CH3:16]>ClCCl>[C:15]([O:19][C:20]([CH2:22][NH:23][CH2:12][CH2:11][N:10]([CH3:8])[C:13](=[O:3])[CH3:14])=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: CNCCNCC(=O)OC(C)(C)C
Reactant: CCN(CC)CC
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Product: CC(=O)N(C)CCNCC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 15 h
Yield: 99.8 %

Procedure:
Under nitrogen atmosphere, acetic anhydride (1.16 ml, 12.3 mmol) and triethylamine (2.28 ml, 16.4 mmol) were added to a dichloromethane (41 ml) solution of [2-(tert-butoxycarbonylmethylamino)ethyl]methylamine (I-202) (1.54 g, 8.18 mmol) with cooling with ice, followed by stirring at room temperature for 15 hours. The solvent was evaporated away under reduced pressure, then the resulting residue was subjected to silica gel column chromatography, and the eluate with dichloromethane/methanol (10:1, v/v) gave the entitled compound (1.88 g, 100%) as a colorless oil.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH:11]1[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[CH:14]=[CH:13][C:12]=1/[C:21](/[CH3:28])=[CH:22]/[C:23](OCC)=[O:24]>C1(C)C=CC=CC=1.C(Cl)Cl>[CH:11]1[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[CH:14]=[CH:13][C:12]=1/[C:21](/[CH3:28])=[CH:22]/[CH2:23][OH:24]
Reactant: CCOC(=O)/C=C(\C)c1ccc2c(c1)CCCC2
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: C/C(=C\CO)c1ccc2c(c1)CCCC2
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 86 %

Procedure:
A solution of diisobutylaluminum hydride in toluene (1.5M, 25 ml) was added dropwise to a solution of ethyl (E)-3-(5,6,7,8-tetrahydro-2-naphtyl)crotonate (3.72 g) in CH2Cl2 at −78° C. and the mixture was stirred at −78° C. for 15 minutes. The reaction mixture was washed with 1N HCl and brine, dried and concentrated to give the titled compound (2.65 g) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:19]2[C:18](=[O:20])[NH:17][CH:16]=[N:15][C:14]=2[N:13]([CH3:21])[C:12](=[O:22])[CH:11]=1.C(=O)([O-])[O-].[K+].[K+].ClC1C=CC([N+]([O-])=O)=CC=1[N+]([O-])=O.[C:42]([O:46][CH2:47][CH2:48][O:49]N)([CH3:45])([CH3:44])[CH3:43]>CC(N(C)C)=O>[C:42]([O:46][CH2:47][CH2:48][O:49][N:17]1[C:18](=[O:20])[C:19]2[C:10]([NH:9][C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])=[CH:11][C:12](=[O:22])[N:13]([CH3:21])[C:14]=2[N:15]=[CH:16]1)([CH3:45])([CH3:44])[CH3:43]
Reactant: Cn1c(=O)cc(Nc2ccc(I)cc2F)c2c(=O)[nH]cnc21
Reactant: CC(C)(C)OCCON
Agent: O=C([O-])[O-]
Agent: O=[N+]([O-])c1ccc(Cl)c([N+](=O)[O-])c1
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: Cn1c(=O)cc(Nc2ccc(I)cc2F)c2c(=O)n(OCCOC(C)(C)C)cnc21
Temperature: 80 °C
Reaction time: 1 h
Yield: 12 %

Procedure:
Compound 5F (250 mg, 0.61 mmol), potassium carbonate (209 mg, 1.51 mmol) and 1-chloro-2,4-dinitrobenzene (307 mg, 1.51 mmol) were stirred in DMA at 80° C. for 1.5 h. O-(2-tert-Butoxy-ethyl)-hydroxylamine was added at r.t and the reaction was stirred for 1 h at 80° C. Purification by prep-HPLC gave 43 mg (12%) of the title compound as an off-white solid. MS (ES) [m+H] calc'd for C20H22FIN4O4, 529; found 529.
Reaction SMILES: C(N(CC)CC)C.[Cl-].[Br:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([OH:21])=[C:15]([NH3+:20])[CH:16]=[N:17]2)=[CH:12][CH:11]=1.[C:22]([O:25][CH2:26][C:27](Cl)=[O:28])(=[O:24])[CH3:23]>ClCCl>[C:22]([O:25][CH2:26][C:27]([NH:20][C:15]1[CH:16]=[N:17][C:18]2[C:13]([C:14]=1[OH:21])=[CH:12][CH:11]=[C:10]([Br:9])[CH:19]=2)=[O:28])(=[O:24])[CH3:23]
Reactant: [NH3+]c1cnc2cc(Br)ccc2c1O
Reactant: CC(=O)OCC(=O)Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OCC(=O)Nc1cnc2cc(Br)ccc2c1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 80.7 %

Procedure:
Triethylamine (161 g, 1.59 mol) was added to a suspension of 7-bromo-4-hydroxyquinolin-3-aminium chloride (224 g, 0.815 mol) in dichloromethane (2.25 L), and the mixture was cooled to approximately 0° C. Acetoxyacetyl chloride (112 g, 0.820 mol) was added over a period of one hour. The reaction was stirred at room temperature for one hour and then allowed to stand for three days. A solid was present and was isolated by filtration and pressed dry. The solid was stirred in deionized water (2 L) for two hours, isolated by filtration, dried overnight on the filter funnel, and further dried in a vacuum oven at 60 to 70° C. to provide 223 g of 2-[(7-bromo-4-hydroxyquinolin-3-yl)amino]-2-oxoethyl acetate as a reddish brown solid.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]2[N:37]=[CH:36][C:35]([C:38]([OH:40])=O)=[CH:34][N:33]=2)[CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.[F:50][C:51]([F:64])([F:63])[C:52]1[NH:53][C:54]2[C:59]([CH:60]=1)=[CH:58][C:57]([CH2:61][NH2:62])=[CH:56][CH:55]=2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH3:25][CH:26]1[CH2:27][CH2:28][N:29]([C:32]2[N:33]=[CH:34][C:35]([C:38]([NH:62][CH2:61][C:57]3[CH:58]=[C:59]4[C:54](=[CH:55][CH:56]=3)[NH:53][C:52]([C:51]([F:64])([F:50])[F:63])=[CH:60]4)=[O:40])=[CH:36][N:37]=2)[CH2:30][CH2:31]1
Reactant: NCc1ccc2[nH]c(C(F)(F)F)cc2c1
Reactant: CC1CCN(c2ncc(C(=O)O)cn2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC1CCN(c2ncc(C(=O)NCc3ccc4[nH]c(C(F)(F)F)cc4c3)cn2)CC1
Reaction time: 16 h

Procedure:
To a stirred solution of HATU (34.4 mg, 0.090 mmol) in 1 ml DMF was added (2-(4-methyl-1-piperidinyl)-5-pyrimidinecarboxylic acid) (Matrix Scientific, 20 mg, 0.090 mmol) in 0.5 ml DMF, followed by DIPEA (0.016 ml, 0.090 mmol) and finally {[2-(trifluoromethyl)-1H-indol-5-yl]methyl}amine (Intermediate 4, 22.66 mg, 0.090 mmol) in 1 ml DMF. Stirring was continued for 16 hours. 1M citric acid solution (10 ml) was added and the mixture was then extracted with ethyl acetate (20 ml). The organic extract was then washed with 1M citric acid solution (10 ml), brine (10 ml), dried (MgSO4), filtered and evaporated to dryness. The resulting residues where then purified on the MDAP to dryness to give the title compound (19 mg);
Reaction SMILES: [CH2:1]([P:3]([O-:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].N12CCCN=C1CCCCC2.Cl[CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25]>C1C=CC([P]([Ni]([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.C1(C)C=CC=CC=1>[CH2:1]([P:3]([CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: CCCCOP([O-])CC
Reactant: CC(C)=CCCl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Ni]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1
Product: CCCCOP(=O)(CC)CC=C(C)C
Yield: 75.8 %

Procedure:
At room temperature, a three-neck flask equipped with stirrer and high-performance condenser is initially charged with 400 g of toluene and this initial charge is devolatilized by stirring and passing nitrogen through it. Then, under nitrogen, 6.65 g (6 mmol) of tetrakis(triphenylphosphine)nickel and 30 g (0.2 mol) of butyl ethylphosphonite (produced as in Example 2) and 30.4 g (0.2 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene are added followed by the dropwise addition of 20.9 g (0.2 mol) of 1-chloro-3-methyl-2-butene. Following a reaction time of 5 hours, the reaction solution is passed for purification through a column charged with Deloxan® THP Hand the solvent is removed in vacuo. The product is purified by column chromatography to obtain 33.1 g (76% of theory) of butyl ethyl(3-methyl-2-butenyl)phosphinate as colorless oil.
Reaction SMILES: C1(C)C=CC(S(O[C@H:11]([CH2:13]/[CH:14]=[CH:15]/[C:16]2[CH:17]=[N:18][CH:19]=[C:20]([O:22][CH:23]([CH3:25])[CH3:24])[CH:21]=2)[CH3:12])(=O)=O)=CC=1.[CH3:27][NH2:28]>>[CH3:27][NH:28][C@@H:11]([CH2:13]/[CH:14]=[CH:15]/[C:16]1[CH:17]=[N:18][CH:19]=[C:20]([O:22][CH:23]([CH3:25])[CH3:24])[CH:21]=1)[CH3:12]
Reactant: Cc1ccc(S(=O)(=O)O[C@@H](C)C/C=C/c2cncc(OC(C)C)c2)cc1
Reactant: CN
Product: CN[C@H](C)C/C=C/c1cncc(OC(C)C)c1
Temperature: 100 °C

Procedure:
A mixture of (2S)-(4E)-5-(5-isopropoxy-3-pyridyl)-4-penten-2-ol p-toluenesulfonate (10.00 g, 26.63 mmol) and methylamine (50 mL, 2.0M solution in THF) was heated at 100° C. for 10 h in a sealed glass tube. The mixture was cooled to ambient temperature and concentrated under reduced pressure on a rotary evaporator. The crude product was treated with saturated NaHCO3 solution (50 mL) and extracted with chloroform (4×50 mL). The combined chloroform extracts were dried (K2CO3), filtered, and concentrated by rotary evaporation to afford a dark-brown oil (3.50 g). The crude product was purified by repeated (twice) column chromatography on silica gel, eluting with chloroform-methanol (95:5, v/v). Selected fractions were combined, concentrated by rotary evaporation affording a light-brown oil (2.50 g). The oil was further purified by vacuum distillation using a short-path distillation apparatus, collecting 2.05 g (32.9%) of a colorless oil, bp 98-100° C. at 0.04 mm Hg.
Reaction SMILES: [N+:1](=[C:3]1[C:23](=[O:24])[CH2:22][CH2:21][C@@:20]2([CH3:25])[C@H:4]1[CH2:5][CH2:6][C@@H:7]1[C@@H:19]2[CH2:18][CH2:17][C@@:16]2([CH3:26])[C@H:8]1[CH2:9][CH2:10][C@@H:11]2[C@@H:12]([CH3:15])[CH2:13][OH:14])=[N-:2].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl.CCOCC>[N+:1](=[C:3]1[C:23](=[O:24])[CH2:22][CH2:21][C@@:20]2([CH3:25])[C@H:4]1[CH2:5][CH2:6][C@@H:7]1[C@@H:19]2[CH2:18][CH2:17][C@@:16]2([CH3:26])[C@H:8]1[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH:13]=[O:14])[CH3:15])=[N-:2]
Reactant: C[C@@H](CO)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C(=[N+]=[N-])C(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: C[C@@H](C=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C(=[N+]=[N-])C(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To 60 mg of (5α,20R)-4-diazo-21-hydroxy-20-methyl-pregnane-3-one in 5 ml of dichloromethane is added 60 mg of pyridinium chlorochromate and the mixture is stirred for 16 hours at room temperature. It is then diluted with ether and filtered through a small column of silica gel in ether. Evaporation of the solvent leaves a solid which is recrystallized from ether to give (5α,20R)-4-diazo-3-oxopregnane-20-carboxaldehyde which melts with decomposition.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([C:18]2[O:19][C:20]([C:23]3[N:28]=[C:27]([C:29]([O:31]C)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[CH:21][N:22]=2)=[O:17])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Cl>C1COCC1.O.CCOC(C)=O>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][C:16]([C:18]2[O:19][C:20]([C:23]3[N:28]=[C:27]([C:29]([OH:31])=[O:30])[CH:26]=[CH:25][CH:24]=3)=[CH:21][N:22]=2)=[O:17])=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1cccc(-c2cnc(C(=O)CCc3ccc(Oc4ccccc4)cc3)o2)n1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cccc(-c2cnc(C(=O)CCc3ccc(Oc4ccccc4)cc3)o2)n1
Yield: 91.2 %

Procedure:
Methyl 6-(2-(3-(4-phenoxyphenyl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (356 mg, 0.831 mmol) was dissolved in THF/H2O (3:2, 75 mL) and LiOH (59 mg, 2.5 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 2 h before the addition of 1 N HCl to adjust the solution to an acidic pH to quench the reaction. The reaction solution was diluted with EtOAc and the organic and aqueous layers were separated. The aqueous layer was extracted with EtOAc (3×). The organic phases were combined and washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 1% AcOH/EtOAc) to provide 6-(2-(3-(4-phenoxyphenyl)propanoyl)oxazol-5-yl)pyridine-2-carboxylic acid as a light yellow solid (314 mg, 91%): 1H NMR (THF-d8, 500 MHz) δ 8.11-8.03 (m, 4H), 7.30-7.25 (m, 4H), 7.03 (t, 1H, J=8.0 Hz), 6.94 (d, 2H, J=8 Hz), 6.91 (d, 2H, J=8.5 Hz), 3.43 (t, 2H, J=7.5 Hz), 3.04 (t, 2H, J=7.5 Hz); 13C NMR (THF-d8, 500 MHz) δ 187.3, 165.7, 158.9, 156.7, 153.6, 150.1, 147.2, 139.7, 137.1, 130.7, 130.6, 128.7, 125.5, 123.8, 123.7, 120.0, 119.4, 41.7, 29.8; HR ESI-TOF m/z 415.1284 (M+H+, C24H18N2O5, requires 415.1288).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH2:10])[CH:3]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.O1CCOC[CH2:24]1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:10][CH2:24][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:3]=1
Reactant: C1COCCN1
Reactant: C1COCCO1
Reactant: C=C(c1ccccc1)c1cc(C)ccc1O
Product: Cc1ccc(O)c(C(CCN2CCOCC2)c2ccccc2)c1
Yield: 82 %

Procedure:
0.421 g (2.0 mmole) 4-methyl-2-(1-phenyl-vinyl)-phenol, 0.10 ml (1.15 mmole) morpholine, 6.0 mg (12 μmole) [RhCl(cod)]2 and 10 ml abs. dioxane are agitated in a pressure vessel for 3 days at 120° C. and under a pressure of 90 bar synthesis gas (CO:H2=7.2). Following cooling and relieving of the pressure vessel, the reaction solution undergoes absorptive filtering (eluant: diethylether, then ethanol) through aluminium oxide (activity II-III, basic). Following removal of the solvent, the cleaning of the raw product takes place by column chromatography on silica gel with cyclohexane/MTBE (ratio of volumes=1/1) as the eluant. 255 mg (0.82 mmole, 82%) 4-methyl-2-(3-morpholin-4-yl-1-phenyl-propyl)-phenol are obtained.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=[O:3])[CH3:2].[C-:8]#[N:9].[K+].[C:11]1([CH3:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:5]([O:4][CH2:1][C:2]1[CH:15]=[CH:16][CH:11]=[CH:12][CH:13]=1)(=[O:7])[CH3:6].[C:1]([O:4][CH2:17][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:8]#[N:9])(=[O:3])[CH3:2]
Reactant: Cc1ccccc1
Reactant: [C-]#N
Reactant: CC(=O)OC(C)=O
Agent: [K+]
Product: CC(=O)OCc1ccccc1
Product: CC(=O)OCc1ccccc1C#N
Yield: 72 %
Yield: 25 %

Procedure:
A stirred 2-liter autoclave is charged with toluene (400g), cobaltous 2-ethyl hexanoate (2g), acetic anhydride (50g) and potassium cyanide (25g) in that order in the confines of a well ventilated hood. The autoclave is sealed, flushed with N2 and heated to 150° whereupon the N2 pressure of 176 psig is increased to 220 psig with oxygen. The oxygen pressure is maintained at 45 psig during the reaction and at completion of the reaction the product is isolated by distillation. At 1.5% conversion of the toluene there is a 25% yield of benzyl acetate and 72% yield of 2-cyanobenzyl acetate based on the toluene converted.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N+:16]([O-])([OH:18])=[O:17].OS(O)(=O)=O.O>CC(O)=O>[C:1]([C:5]1[CH:10]=[C:9]([N+:16]([O-:18])=[O:17])[C:8]([OH:11])=[C:7]([C:12]([F:13])([F:14])[F:15])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=[N+]([O-])O
Reactant: CC(C)(C)c1ccc(O)c(C(F)(F)F)c1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)c1cc([N+](=O)[O-])c(O)c(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
4-tert-Butyl-2-trifluoromethyl-phenol (70 mg, 0.32 mmol) was dissolved in 3 mL AcOH/1.5 mL water and cooled to 0° C. HNO3 (1.5 mL) and catalytic H2SO4 were added and the reaction was allowed to warm to room temperature. Stirring was continued overnight, after which water was added and the compound was extracted into EtOAc. The organic layer was dried over MgSO4 and concentrated to yield 34 mg of final compound. Calculated mass=263. Observed mass=264
Reaction SMILES: [CH2:1]([CH2:6][CH2:7][NH2:8])[CH2:2][CH2:3][CH2:4][NH2:5].[C:9](=[O:20])([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])N.N>>[CH2:12]([O:11][C:9]([NH:5][CH2:4][CH2:3][CH2:2][CH2:1][CH2:6][CH2:7][NH:8][C:9]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:20])=[O:20])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[CH2:1]([CH2:6][CH2:7][NH2:8])[CH2:2][CH2:3][CH2:4][NH2:5]
Reactant: CCCCCCCCOC(N)=O
Agent: N
Agent: NCCCCCCN
Product: CCCCCCCCOC(=O)NCCCCCCNC(=O)OCCCCCCCC
Temperature: 110 °C

Procedure:
Agitated in a reaction vessel are 116 parts of 1,6-hexamethylenediamine with 380 parts of O-octyl carbamate and 130 parts of n-octanol-(1) at a reflux temperature of 185° C.-205° C. for 2 hours while the ammonia is removed by distillation. At this point, an additional 500 parts of n-octanol-(1) are allowed to flow into the reaction mixture and the reaction is continued at reflux temperature for 7 hours. The reaction mixture, cooled to 110° C., is filtered, and the reaction product is allowed to crystallize by cooling. By filtration, washing with n-octanol-(1) and drying, 388 parts of 1,6-bis(octoxycarbonylamino)hexane are obtained corresponding with 90.6 percent theory relative to 1,6-hexamethylenediamine. The melting point is 107° C.-109° C.
Reaction SMILES: [F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]2[C:11](=[CH2:12])[C:10]([CH3:14])([CH3:13])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:25])C=1.[OH-].[Ca+2].[OH-]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]2[C:11]3([O:25][CH2:12]3)[C:10]([CH3:13])([CH3:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C1C(Cc2ccc(F)cc2)CCC1(C)C
Agent: [Ca+2]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: CC1(C)CCC(Cc2ccc(F)cc2)C12CO2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Into 170 ml of chloroform, 17 g of 5-[4-fluorobenzyl)-2,2-dimethyl-1-methylenecyclopentane (the compound No. shown in Table 3) were dissolved, and then, 27.1 g of m-chloroperbenzoic acid were added to the mixture within 10 min, and the thus obtained mixture was stirred for 2 hours at room temperature. In the next place, 25.4 g of calcium hydroxide were added to the mixture within 10 min, and the mixture was stirred for 30 min at room temperature.