Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC([O-])(C)C.[K+].C1COCC1.[OH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([CH2:25][C:26]([NH2:28])=[O:27])=[CH:17]1.C[O:30][C:31](=O)[C:32]([C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:42]=1[N:41](COCC[Si](C)(C)C)[CH:40]=[CH:39]2)=O.Cl>CN(C=O)C.CCOC(C)=O>[OH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]2[C:26](=[O:27])[NH:28][C:31](=[O:30])[C:32]=2[C:34]2[CH:35]=[CH:36][CH:37]=[C:38]3[C:42]=2[NH:41][CH:40]=[CH:39]3)=[CH:17]1
Reactant: NC(=O)Cc1cn(CCCO)c2ccccc12
Reactant: COC(=O)C(=O)c1cccc2ccn(COCC[Si](C)(C)C)c12
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1NC(=O)C(c2cccc3cc[nH]c23)=C1c1cn(CCCO)c2ccccc12
Reaction time: 0.25 h
Yield: 51 %

Procedure:
A 1.0 M solution of KOtBu in THF (8.1 mL, 8.1 mmol) was added to a solution of 2-(1-3-hydroxypropyl-1H-indol-3-yl)-acetamide (586 mg, 2.52 mmol) and {1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-7-yl}-oxo-acetic acid methyl ester (770 mg, 2.31 mmol) in DMF (30 mL). The initially clear orange-red solution turned deep red over 15 min, and was then heated to 65 C. for 18 h. 1N HCl was added, the mixture stirred 8 h and then the volume was reduced to ˜20 mL. The residue was poured into EtOAc/0.1 N HCl and the aqueous layer was separated and extracted with EtOAc. The EtOAc solutions were combined and washed with water, saturated aq NaHCO3 and brine (3×), dried (MgSO4), filtered and concentrated onto SiO2. Flash chromatography (8:2 EtOAc:hexanes) afforded a red solid that was dried at 75° C. for overnight giving the title compound (454 mg, 51%) as a bright red solid. 1H NMR (400 MHz, DMSO-d6) 11.04 (s, 1H), 10.71 (s, 1H), 8.03 (s, 1H), 7.56–7.62 (m, 1H), 7.41 (d, J=8 Hz, 1H), 7.20 (dd, J=3, 3 Hz, 1H), 6.94–7.0 (m, 3H), 6.45 (dd, J=8, 8 Hz, 1H), 6.40–6.43 (m, 1H), 6.11 (d, J=8 Hz, 1H), 4.64 (t, J=5 Hz, 1H), 4.29 (t, J=7 Hz, 2H), 3.38 (s, 2H), 1.88 (m, 2H). MS (electrospray, m/z) 386.2 (M++1), 384.2 (M−−1). HRMS 386.1504 (M++1, calcd for C23H20N3O3 386.1505)
Reaction SMILES: [Li+].[OH-].C([O:5][C:6](=[O:37])[CH2:7][C@@H:8]([C:35]#[CH:36])[NH:9][C:10]([C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18](=[O:34])/[CH:19]=[CH:20]\[CH:21]2[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]2)[CH2:13]1)=[O:11])C.CCO.O>O1CCCC1>[NH:24]1[CH2:23][CH2:22][CH:21](/[CH:20]=[CH:19]\[C:18]([N:14]2[CH2:15][CH2:16][CH2:17][C@@H:12]([C:10]([NH:9][C@H:8]([C:35]#[CH:36])[CH2:7][C:6]([OH:37])=[O:5])=[O:11])[CH2:13]2)=[O:34])[CH2:26][CH2:25]1
Reactant: C#C[C@H](CC(=O)OCC)NC(=O)[C@@H]1CCCN(C(=O)/C=C\C2CCN(C(=O)OC(C)(C)C)CC2)C1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: C#C[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN(C(=O)/C=C\C2CCNCC2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 67.7 %

Procedure:
1N aqueous LiOH (3.0 ml) was added to a solution of N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(Z)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine ethyl ester (1.0 g) in tetrahydrofuran (5 ml)-EtOH (5 ml) at 0° C. The reaction mixture was stirred for 2 hours at room temperature, then water was added, and the whole was washed with diethyl ether. The aqueous layer was made acidic with 20% aqueous KHSO4, and extracted with ethyl acetate. The organic layer was dried over MgSO4, evaporated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and 4N HCl in ethyl acetate (5.1 ml) was added. The reaction mixture was stirred for 2 hours and diethyl ether was added. The precipitates were collected with filtration and dissolved with water. The solution was neutralized with saturated aqueous NaHCO3 and purified by HP-20 resin eluting with isopropanol/water=(0-30%) to give N-[(R)-1-[3-(4-piperidyl)-(Z)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine (0.5 g, 67.8%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:16]([CH:17]([OH:19])[CH3:18])=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[C:17]([C:16]1[C:12]([O:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:13][O:14][C:15]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)(=[O:19])[CH3:18]
Reactant: CC(O)c1c(OCCNC(=O)OC(C)(C)C)noc1-c1ccccc1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(=O)c1c(OCCNC(=O)OC(C)(C)C)noc1-c1ccccc1
Reaction time: 24 h
Yield: 87.2 %

Procedure:
3-(2-(N-tert-Butoxycarbonylamino)ethoxy)-4-(1-hydroxyethyl)-5-phenylisoxazole (0.3 g) was dissolved in methylene chloride (3 ml), and pyridinium dichromate (0.49 g) was added thereto at room temperature, followed by stirring of the resulting mixture at the same temperature for 24 hours. After the reaction, insolubles were filtered and the solvent of the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain the title compound (0.26 g, 87%) as a colorless powder.
Reaction SMILES: C1(C)C=CC=CC=1.[CH3:8][C:9]1([CH3:19])[C:14](=[O:15])[CH2:13][C:12](=[O:16])[C:11]([CH3:18])([CH3:17])[O:10]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:32][C:33]1[CH:38]=[CH:37][C:36]([Pb+3])=[C:35]([CH2:40][CH3:41])[CH:34]=1.Cl>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[Br:32][C:33]1[CH:38]=[CH:37][C:36]([CH:13]2[C:14](=[O:15])[C:9]([CH3:19])([CH3:8])[O:10][C:11]([CH3:18])([CH3:17])[C:12]2=[O:16])=[C:35]([CH2:40][CH3:41])[CH:34]=1
Reactant: CCc1cc(Br)ccc1[Pb+3]
Reactant: CC1(C)OC(C)(C)C(=O)CC1=O
Agent: CC(=O)[O-]
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CCc1cc(Br)ccc1C1C(=O)C(C)(C)OC(C)(C)C1=O
Temperature: 80 °C
Reaction time: 4 h

Procedure:
4-Dimethylaminopyridine (3.13 g, 25.7 mmol) and toluene (10 ml) are added to a solution of 2,2,6,6-tetramethylpyran-3,5-dione (0.87 g, 5.13 mmol) in chloroform (40 ml) and the reaction mixture is heated to 80° C. 4-Bromo-2-ethylphenyllead triacetate (3.50 g, 6.16 mmol) is added portionwise over 5 minutes, and once the addition is complete the reaction mixture is stirred at 80° C. for a further 4 hours. The mixture is cooled to room temperature, 2M aqueous hydrochloric acid (40 ml) is added, and the mixture is stirred vigorously for 20 minutes, then filtered through a small plug of diatomaceous earth, washing with dichloromethane (40 ml). The organic phase is separated, and the aqueous phase is extracted with dichloromethane (2×40 ml). The organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-(4-bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:13]([C:14]#[N:15])=[C:12]([CH:16](OC)[O:17]C)[NH:11][C:10]2=[N:21][NH:22][CH:23]=[C:9]12>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:13]([C:14]#[N:15])=[C:12]([CH:16]=[O:17])[NH:11][C:10]2=[N:21][NH:22][CH:23]=[C:9]12
Reactant: COC(OC)C1=C(C#N)C(c2ccccc2Cl)c2c[nH]nc2N1
Solvent: O=C(O)C(F)(F)F
Product: N#CC1=C(C=O)Nc2n[nH]cc2C1c1ccccc1Cl
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 50.2 %

Procedure:
4-(2-Chlorophenyl)-5-cyano-6-dimethoxymethyl-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine (4.4 g) was added to trifluoroacetic acid (20 ml) under ice-cooling and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated under reduced pressure and crystallized from ethyl acetate (50 ml) to give the title compound (1.9 g) as yellow crystals.
Reaction SMILES: O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH:46][C:47](=[O:56])/[CH:48]=[CH:49]/[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH:43]=[CH:44][CH:45]=2)=[N:8]1>Cl.O1CCOCC1>[NH:18]1[CH:19]=[N:20][C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([NH:46][C:47](=[O:56])/[CH:48]=[CH:49]/[C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[CH:43]=[CH:44][CH:45]=2)=[N:17]1
Reactant: O=C(/C=C/c1ccccc1)Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Agent: Cl
Solvent: C1COCCO1
Product: O=C(/C=C/c1ccccc1)Nc1cccc(-c2n[nH]c3ccc(-c4nc[nH]n4)cc23)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 33 %

Procedure:
(2E)-N-(3-{1-Perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)](1H-indazol-3-yl)}phenyl)-3-phenylprop-2-enamide was dissolved in 4 mL of 4.0 N HCl in 1,4-dioxane and the reaction was stirred at room temperature overnight. After neutralization with aqueous NaHCO3, the compound precipitated out of solution. The solid was collected by filtration and was purified by preparative HPLC. (0.036 g, 33% yield over 2 steps): 1H NMR (CD3OD) δ 8.7 (s, 1H), 8.3 (br s, 1H), 8.1 (br d, 1H), 7.8–7.6 (m, 6H), 7.54 (t, 1H), 7.45–7.4 (m, 3H), 6.85 (d, 1H); ES-MS (m/z) 407 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:5]=1[C:6](=[O:19])[C:7]1[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=1[C:13]2=[O:18])([O-])=O.[OH-].[Na+].ONC1C2C(=O)C3C(=CC=CC=3)C(=O)C=2C=CC=1.[H][H].O=O>[Pd].COCCO>[NH2:1][C:4]1[C:5]2[C:6](=[O:19])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13](=[O:18])[C:14]=2[CH:15]=[CH:16][CH:17]=1
Reactant: [H][H]
Reactant: O=C1C2=C(CCCC2)C(=O)c2c1cccc2[N+](=O)[O-]
Agent: [Pd]
Agent: O=C1c2ccccc2C(=O)c2c(NO)cccc21
Agent: O=O
Solvent: COCCO
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a mixture of 260 grams of 5-nitrotetrahydroanthraquinone and 10,100 grams of methyl cellosolve were added 2.6 grams of a 5% palladium on carbon catalyst and 300 grams of a 20% aqueous sodium hydroxide solution, followed by agitating at room temperature for 1 hour. The color of the solution was green inherent to 1-hydroxylaminoanthraquinone. Part of the reaction solution was sampled and subjected to a thin layer chromatography, by which it was recognized that almost all of the starting 5-nitro compound was converted to 1-hydroxylaminoanthraquinone. Thereafter, hydrogen was fed into the reaction solution for hydrogenation and 2 mols of hydrogen was absorbed in each 1 mol of the 5-nitro compound. The hydrogen in the reactor was replaced by nitrogen, followed by introduction of air into the reaction solution for oxidation. Upon determination, it was found that oxygen was absorbed in an amount of 0.5 mol per mol of the 5-nitro compound. The reaction solution turned reddish orange with a reddish orange precipitate. The precipitate was separated by filtration, washed with water and dried to obtain 220 grams of 1-aminoanthraquinone having a purity of 98%.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([Cl:11])[C:5]=1[OH:12].[Br:13][CH2:14][CH2:15]Br>O.C(O)C>[Br:13][CH2:14][CH2:15][O:12][C:5]1[C:4]([Cl:3])=[CH:9][C:8]([Cl:10])=[CH:7][C:6]=1[Cl:11]
Reactant: BrCCBr
Reactant: Oc1c(Cl)cc(Cl)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Clc1cc(Cl)c(OCCBr)c(Cl)c1
Yield: 67.4 %

Procedure:
A solution of sodium hydroxide (7.8 g, 0.195 mol) in water (20 ml) was added to a solution of 2,4,6-trichlorophenol (38.0 g, 0.192 mol) in ethanol (200 ml). 1,2-dibromoethane (47 g, 0.25 mol) was then added and the resultant mixture was refluxed overnight. On cooling, the solid was filtered off and the filtrate concentrated under reduced pressure. Ether was added to the residue and the solution was then washed with dilute sodium hydroxide solution and dried over anhydrous magnesium sulphate. After removal of the solvent by evaporation, the residue was recrystallised from ethanol to give 1-bromo-2-(2,4,6-trichlorophenoxy)ethane as a white solid (39.4 g). A mixture of the 1-bromo-2-(2,4,6-trichlorophenoxy) ethane (20.0 g, 0.066 mol), triethylamine (6.7 g, 0.066 mol) and propylamine (3.9 g, 0.066 mol) in ethanol (500 ml) was then refluxed overnight. After removal of the solvent by evaporation, the residue was dissolved in ether, washed with water and dried (MgSO4). Evaporation of the solvent left an oil which, after flash chromatography on silica gel using chloroform as the eluant, yielded N-propyl-N-2-(2,4,6-trichlorophenoxy)ethylamine as an oil (12.6 g).
Reaction SMILES: O=S(Cl)[Cl:3].[Cl:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([Cl:14])[C:11]=1[CH2:12]O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Cl:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([Cl:14])[C:11]=1[CH2:12][Cl:3]
Reactant: O=S(Cl)Cl
Reactant: OCc1c(Cl)cncc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: ClCc1c(Cl)cncc1Cl
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
SOCl2 (2.3 mL, 32 mmol) was added dropwise to a stirred solution of (3,5-dichloropyridin-4-yl)-methanol (2.83 g, 15.9 mmol) in DCM (20 mL) over 10 min. After stirring for 35 min at room temperature, saturated aqueous Na2CO3 solution (40 mL) and DCM (60 mL) was added to the reaction mixture. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with EA/hexane 1:4) to give the title compound. MS (m/z): 196.0 [M+H+].
Reaction SMILES: C(OC([NH:11][CH:12]1[N:18]=[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[N:14]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:13]1=[O:33])=O)C1C=CC=CC=1.Br>C(Cl)Cl>[NH2:11][CH:12]1[N:18]=[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[N:14]([CH2:29][CH:30]([CH3:31])[CH3:32])[C:13]1=[O:33]
Reactant: CC(C)CN1C(=O)C(NC(=O)OCc2ccccc2)N=C(c2ccccc2)c2ccccc21
Agent: Br
Solvent: ClCCl
Product: CC(C)CN1C(=O)C(N)N=C(c2ccccc2)c2ccccc21

Procedure:
A solution of 3-benzyloxycarbonylamino-1-isobutyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (880 mg, 1.99 mmol) in methylene chloride (10 mL) was cooled to 0° C. and saturated with hydrogen bromide gas. The reaction was refluxed overnight, cooled, saturated with hydrogen bromide and refluxed 3 h. Solvent was evaporated and the reaction worked up with saturated sodium bicarbonate solution and methylene chloride. The title compound was isolated by column chromatography (silica gel, 0 to 10% methanol in methylene chloride gradient elution). Enantiomers were separated on a Chiralpak AS column (silica gel, 30% hexane, 70% ethanol with diethylamine, isocratic elution), yielding enantiomer A of the title compound (91.9 mg) and enantiomer B of the title compound (87.1 mg).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.CCN(CC)CC.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:21][C:5]1[CH:4]=[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[C:2]([N:1]([S:40]([CH3:39])(=[O:42])=[O:41])[S:40]([CH3:39])(=[O:42])=[O:41])=[N:7][C:6]=1[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)[CH2:12][CH2:11]1)=[O:9]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cc(-c2cccc(C(F)(F)F)c2)c(N)nc1C(=O)N1CCC(N2CCCC2)CC1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1cc(-c2cccc(C(F)(F)F)c2)c(N(S(C)(=O)=O)S(C)(=O)=O)nc1C(=O)N1CCC(N2CCCC2)CC1
Temperature: 50 °C
Reaction time: 5 h
Yield: 44.2 %

Procedure:
A solution of 0.22 g (0.5 mmol) of [6-amino-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 7) in 5.0 ml of DMF was treated with 0.43 ml=0.309 g (3.1 mmol) of Et3N and 0.006 g (0.05 mmol) of DMAP. To the stirred solution was added 0.08 ml=0.12 g (1.0 mmol) of methanesulfonyl chloride drop by drop and the reaction mixture was subsequently warmed up to 50° C. After 5 hours, it was poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1) to give 0.13 g (44%) of the title compound as yellow solid. MS: 589.1 (MH+).
Reaction SMILES: [P:1]([O:13][CH2:14][CH2:15][NH:16][S:17]([C:20]1[CH:37]=[CH:36][C:23]2[C:24]3[CH:25]([CH2:34][Cl:35])[CH2:26][NH:27][C:28]=3[CH:29]=[C:30]([N+:31]([O-:33])=[O:32])[C:22]=2[CH:21]=1)(=[O:19])=[O:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:38][O:39][C:40]1[CH:41]=[C:42]2[C:46](=[C:47]([O:51][CH3:52])[C:48]=1[O:49][CH3:50])[NH:45][C:44]([C:53](O)=[O:54])=[CH:43]2.CCN=C=NCCCN(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O>[P:1]([O:13][CH2:14][CH2:15][NH:16][S:17]([C:20]1[CH:37]=[CH:36][C:23]2[C:24]3[CH:25]([CH2:34][Cl:35])[CH2:26][N:27]([C:53]([C:44]4[NH:45][C:46]5[C:42]([CH:43]=4)=[CH:41][C:40]([O:39][CH3:38])=[C:48]([O:49][CH3:50])[C:47]=5[O:51][CH3:52])=[O:54])[C:28]=3[CH:29]=[C:30]([N+:31]([O-:33])=[O:32])[C:22]=2[CH:21]=1)(=[O:19])=[O:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: COc1cc2cc(C(=O)O)[nH]c2c(OC)c1OC
Reactant: CC(C)(C)OP(=O)(OCCNS(=O)(=O)c1ccc2c3c(cc([N+](=O)[O-])c2c1)NCC3CCl)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(=O)N(C)C
Product: COc1cc2cc(C(=O)N3CC(CCl)c4c3cc([N+](=O)[O-])c3cc(S(=O)(=O)NCCOP(=O)(OC(C)(C)C)OC(C)(C)C)ccc43)[nH]c2c(OC)c1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 67.3 %

Procedure:
A mixture of 227 (77 mg, 0.13 mmol), 5,6,7-trimethoxyindole-2-carboxylic acid (44 mg, 0.17 mmol), EDCI (102 mg, 0.52 mmol), and TsOH (5 mg, 0.03 mmol) in DMA (1.5 mL) was stirred at room temperature for 2 h. Ice-cold aqueous NaHCO3 was added and the mixture was extracted with EtOAc (×2). The combined extracts were washed with brine (×2), dried, and the solution was evaporated onto silica Chromatography, eluting with EtOAc/petroleum ether (3:2 then 4:1 then EtOAc alone) gave di(tert-butyl) 2-[({1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indol-7-yl}sulfonyl)amino]ethyl phosphate (228) (71 mg, 66%) as a yellow solid. A sample was triturated with CH2Cl2: mp 231-236° C. (dec.); 1H NMR [(CD3)2SO] δ 11.60 (d, J=1.6 Hz, 1H), 9.24 (s, 1H, 8.87 (d, J=1.7 Hz, 1H), 8.44 (d, J=8.9 Hz, 1H), 8.15 (br s, 1H), 8.01 (dd, J=8.9, 1.8 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 6.98 (s, 1H), 4.96-4.90 (m, 1H), 4.68-4.59 (m, 2H), 4.18-4.07 (m, 2H), 3.95 (s, 3H), 3.87-3.82 (ni 2H), 3.84 (s, 3H), 3.81 (s, 3H), 3.10-3.04 (m, 2H), 1.36 (s, 18H). Anal, (C35H44ClN4O12PS) C, H, N.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([NH:12][C:13]2[C:18]([C:19]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:20]=3)=[CH:17][C:16]([C@H:45]([N:47]3[CH2:52][CH2:51][N:50]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:49][CH2:48]3)[CH3:46])=[CH:15][N:14]=2)[CH:7]=[N:8][C:9]=1[O:10][CH3:11])([CH3:3])[CH3:2].FC(F)(F)S(O)(=O)=O>C(O)(C(F)(F)F)=O>[CH:1]([C:4]1[CH:5]=[C:6]([NH:12][C:13]2[C:18]([C:19]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([NH2:26])[N:20]=3)=[CH:17][C:16]([C@H:45]([N:47]3[CH2:52][CH2:51][N:50]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:49][CH2:48]3)[CH3:46])=[CH:15][N:14]=2)[CH:7]=[N:8][C:9]=1[O:10][CH3:11])([CH3:2])[CH3:3]
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(S(C)(=O)=O)CC4)cnc3Nc3cnc(OC)c(C(C)C)c3)n2)cc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Product: COc1ncc(Nc2ncc([C@@H](C)N3CCN(S(C)(=O)=O)CC3)cc2-c2nc(C)nc(N)n2)cc1C(C)C
Temperature: 80 °C
Yield: 31.5 %

Procedure:
A dark red solution of (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.097 g, 0.124 mmol) and trifluoromethanesulfonic acid (0.055 mL, 0.620 mmol) in 1 mL TFA was sealed and heated to 80° C. for 30 min. The reaction was cooled with ice, then quenched with 10 N NaOH until basic, and partitioned between water and DCM. The aqueous layer was extracted with DCM 2 times, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO (plus a few drops TFA) and purified by RPHPLC, 10-80% ACN/H2O (plus 0.1% TFA); product-containing fractions were concentrated to dryness, then treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted 3×DCM and combined organics dried over sodium sulfate, filtered, and concentrated in vacuo to give (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine as a yellow solid (0.021 g, 0.039 mmol, 31% yield). m/z (ESI, +ve ion) 542 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.58 (br. s., 1H), 8.69 (br. s., 1H), 8.17-8.34 (m, 2H), 7.92 (br. s., 1H), 5.38 (br. s., 2H), 3.97 (s, 3H), 3.47-3.62 (m, 1H), 3.11-3.31 (m, 5H), 2.77 (br. s., 3H), 2.49-2.68 (m, 7H), 1.44 (d, J=6.1 Hz, 3H), 1.27 (d, J=6.8 Hz, 6H).
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.Cl>N1C=CC=CC=1>[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([NH:1][C:2]2[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=2[C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:5])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccccc1C(=O)c1ccccc1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccccc2C(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.3 %

Procedure:
To a stirred solution of 15.0 g of 2-aminobenzophenone in 7.5 cc of pyridine was added 14.5 g of p-toluenesulfonyl chloride under ice-cooling. And the resulting mixture was stirred at room temperature for 16 hours. 2N HCl was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with water and dried over magnesium sulfate. The solvent was distilled off and the crude crystals thus obtained were recrystallized from isopropanol to obtain 22.0 g of compound H. Yield: 82.4%.
Reaction SMILES: [CH3:1][CH:2]([C:4]1[C:5](=[O:21])[CH2:6][C:7]([CH3:20])=[CH:8][CH2:9][CH2:10][C:11]([CH3:19])=[CH:12][CH2:13][CH2:14][C:15]([CH3:18])=[CH:16][CH:17]=1)[CH3:3].[H-].C([Al+]CC(C)C)C(C)C.O>C1(C)C=CC=CC=1>[CH3:19][C:11]1=[CH:12][CH2:13][CH2:14][C:15]([CH3:18])=[CH:16][CH:17]=[C:4]([CH:2]([CH3:1])[CH3:3])[C@@H:5]([OH:21])[CH2:6][C:7]([CH3:20])=[CH:8][CH2:9][CH2:10]1
Reactant: CC1=CC=C(C(C)C)C(=O)CC(C)=CCCC(C)=CCC1
Agent: C/C1=C\C=C(\C(C)C)[C@@H](O)C/C(C)=C/CC/C(C)=C/CC1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: O
Product: CC1=CC=C(C(C)C)[C@@H](O)CC(C)=CCCC(C)=CCC1
Reaction time: 1 h

Procedure:
The ketone compound shown above [2-(1-methylethyl)-5,9,13-trimethyl-2,4,8,12-cyclotetradecatetraen-1-one] (137 mg, 0.48 mmol) was dissolved in dry toluene (2.5 ml). To the solution was added with stirring on a cold bath at -70° C. under argon atmosphere 1M solution of diisobutylaluminum hydride in toluene (0.6 ml). Disappearance of the starting material was confirmed 1 hour later, and the mixture was mixed with 0.25 ml of water. The bath was removed, and the mixture was stirred well, dried over anhydrous magnesium sulfate, stirred, and filtered. The filtrate was concentrated. The residue was chromatographed on a silica gel column (Eluent: n-hexane:ethyl acetate=12:1) to give sarcophytol A (125 mg, 88%).