Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([C:12]#[N:13])[N:3]=1.[NH:14]1[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:15]1.CCN(CC)CC>CN1C(=O)CCC1>[C:12]([C:4]1[N:3]=[C:2]([N:14]2[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:15]2)[C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][CH:10]=2)#[N:13]
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Reactant: N#Cc1cc2ccccc2c(Cl)n1
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)NC1CCN(c2nc(C#N)cc3ccccc23)C1
Temperature: 160 °C

Procedure:
A mixture of 1-chloroisoquinoline-3-carbonitrile (438 mg, 2.322 mmol), tert-butyl pyrrolidin-3-ylcarbamate (519 mg, 2.79 mmol) and Et3N (0.653 mL, 4.64 mmol) in NMP (3 mL) was heated at 160° C. for 30 minutes in a microwave reactor. The crude reaction mixture, which contained the title compound, was used directly in the next step.
Reaction SMILES: [CH2:1]([N:5]1[C:12](=[O:13])[C:11]2[CH2:14][CH:15]3[CH2:17][CH:6]1[CH:7]=[C:8]([S:18]([NH2:21])(=[O:20])=[O:19])[S:9][C:10]=2S3)[CH:2]([CH3:4])[CH3:3].OO[S:24]([O-:26])=[O:25].[K+].CO>O>[CH2:1]([N:5]1[C:12](=[O:13])[C:11]2[CH2:14][CH:15]3[CH2:17][CH:6]1[CH:7]=[C:8]([S:18]([NH2:21])(=[O:20])=[O:19])[S:9][C:10]=2[S:24]3(=[O:26])=[O:25])[CH:2]([CH3:4])[CH3:3]
Reactant: O=S([O-])OO
Reactant: CC(C)CN1C(=O)C2=C3SC(S(N)(=O)=O)=CC1CC(C2)S3
Agent: [K+]
Solvent: O
Solvent: CO
Product: CC(C)CN1C(=O)C2=C3SC(S(N)(=O)=O)=CC1CC(C2)S3(=O)=O
Reaction time: 24 h

Procedure:
5-Isobutyl-4-oxo-3,4,5,6-tetrahydro-2H-2,6-methanothieno[3,2-g]-l,5-thiazocine-8-sulfonamide (2 g, 5.8 mmol) was added to a mixture of Oxone® (10 g, 16.3 mmol) and methanol (25 ml). After 24 hours, the reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×50 ml). After drying over sodium sulfate, the solvent was evaporated under reduced pressure to yield 2.13 of a foam. A sample triturated with 1-chlorobutane gave material with mp 239°-241° C.
Reaction SMILES: C([O:5][C:6](=[O:31])[CH:7]([N:17]=C(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:8][CH:9]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)(C)(C)C.Cl>CO.O>[NH2:17][CH:7]([CH2:8][CH:9]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[C:6]([OH:31])=[O:5]
Reactant: CC(C)(C)OC(=O)C(CC1CCCCCCC1)N=C(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: O
Solvent: CO
Product: NC(CC1CCCCCCC1)C(=O)O
Temperature: 25 °C
Reaction time: 20 h
Yield: 62.1 %

Procedure:
To a solution of 2-(Benzhydrylidene-amino)-3-cyclooctyl-propionic acid tert-butyl ester (2.00 g) in methanol (15 mL) was added 10N HCl solution (30 mL) and the mixture heated to reflux. After 20 h, the mixture was allowed to cool to room temperature, diluted with 20 mL of water, transferred to a separatory funnel and washed with ethyl acetate. The aqueous layer was then neutralized with 10N sodium hydroxide solution and further cooled to 0° C. The white solid was filtered off and air dried to give 590 mg of 2-Amino-3-cyclooctyl-propionic acid.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][C:6]([O:9]C)=[CH:5][C:4]=1[NH:11][C:12](=[O:23])[C:13]1[CH:18]=[C:17]([O:19]C)[CH:16]=[CH:15][C:14]=1[O:21]C.Cl.N1C=CC=CC=1>Cl>[OH:9][C:6]1[CH:7]=[CH:8][C:3]2[O:23][C:12]([C:13]3[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:14]=3[OH:21])=[N:11][C:4]=2[CH:5]=1
Reactant: COc1ccc(OC)c(NC(=O)c2cc(OC)ccc2OC)c1
Agent: Cl
Solvent: c1ccncc1
Product: Oc1ccc(O)c(-c2nc3cc(O)ccc3o2)c1
Temperature: 200 °C
Reaction time: 1 h
Yield: 106.1 %

Procedure:
A mixture of N-(2,5-dimethoxyphenyl)-2,5-dimethoxybenzamide (1.0 g, 3.1 mmol) and pyridine hydrochloride (2.0 g, 17.3 mmol) was stirred at 200° C. for 1 h. The mixture was cooled to room temperature and HCl (10 mL, 2 N) was added. The mixture was then extracted with EtOAc and the organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/EtOAc 2/1) gave a white solid (0.8 g, 76% yield, m.p. 309–311° C.); MS m/e 242 (M−H)+.
Reaction SMILES: [NH2:1][NH:2][C:3]([NH2:5])=[S:4].[CH3:6][C:7]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[C:8]=1[C:9](Cl)=[O:10]>CN(C)C=O.N1C=CC=CC=1>[CH3:6][C:7]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[C:8]=1[C:9]([NH:1][NH:2][C:3]([NH2:5])=[S:4])=[O:10]
Reactant: NNC(N)=S
Reactant: Cc1cc(C)c(C(=O)Cl)c(C)c1
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: Cc1cc(C)c(C(=O)NNC(N)=S)c(C)c1
Temperature: 80 °C

Procedure:
37.25 g of thiosemicarbazide was dissolved in 400 ml dimethylformamide and 32.05 g of pyridine, after which 74 g of 2,4,6-trimethylbenzoyl chloride was added at 0° C. in 20 minutes. The reaction mixture was heated at 80° C. for 2 hours and then concentrated to three-quarters in vacuo and the remaining mixture was poured into 1500 ml of cold water. The resulting white precipitate was filtered, washed in water and dried.
Reaction SMILES: CO[C:3]([CH2:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C:15]([OH:17])=O)=[O:7])=O.[C:18]1([NH2:25])[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[NH2:24]>>[NH:24]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:25]=[C:3]1[C:5]1[C:6](=[O:7])[NH:8][C:9]2[C:14]([C:15]=1[OH:17])=[CH:13][CH:12]=[N:11][CH:10]=2
Reactant: Nc1ccccc1N
Reactant: COC(=O)CC(=O)Nc1cnccc1C(=O)O
Product: O=c1[nH]c2cnccc2c(O)c1-c1nc2ccccc2[nH]1
Temperature: 150 °C

Procedure:
3-[2-(Methoxycarbonyl)acetylamino]pyridine-4-carboxylic acid (1.1 equivalents) was combined with 1,2-phenylenediamine (1.0 equivalent) and heated at 150° C. for 3 hours. The crude product was purified by reversed-phase HPLC (DMSO/5% TFA). LC/MS m/z 279.3 (MH+), Rt 1.73 minutes.
Reaction SMILES: [H-].[Na+].C1(CC[OH:11])C=CC=CC=1.[NH2:12][C:13]1[N:14]=[C:15]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:16]([C:23]2[CH:24]=[CH:25][C:26](=[O:30])[N:27]([CH3:29])[N:28]=2)=[N:17][C:18]=1S(C)(=O)=O.Cl>>[NH2:12][C:13]1[N:14]=[C:15]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:16]([C:23]2[CH:24]=[CH:25][C:26](=[O:30])[N:27]([CH3:29])[N:28]=2)=[N:17][C:18]=1[OH:11]
Reactant: Cn1nc(-c2nc(S(C)(=O)=O)c(N)nc2-c2ccccc2)ccc1=O
Reactant: OCCc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Product: Cn1nc(-c2nc(O)c(N)nc2-c2ccccc2)ccc1=O
Temperature: 27.5 °C
Reaction time: 0.5 h

Procedure:
To a suspension of NaH (60% in oil suspension) (33.6 mg) in 1,2-dimethyl-2-imidazolidinone (0.6 ml) was added 2-phenylethanol (0.101 ml) and the mixture was stirred at 25-30° C. for 30 minutes. 6-[5-Amino-6-(methylsulfonyl)-3-phenyl-2-pyrazinyl]-2-methyl-3(2H)-pyridazinone (150 mg) was added and the mixture was heated at 100-105° C. for 15 hours. To the mixture was added 0.1N HCl (3 ml) and a precipitate was collected by filtration. The precipitate was suspended in CHCl3 and collected by filtration to give 6-(5-amino-6-hydroxy-3-phenyl-2-pyrazinyl)-2-methyl-3(2H)-pyridazinone (60 mg). The CHCl3 solution was dried over MgSO4, concentrated under reduced pressure and purified by column chromatography on silica gel eluting with a mixture of n-hexane and EtOAc (50:50 v/v) to give a solid. The solid was suspended in acetone and collected by filtration to give 6-[5-amino-3-phenyl-6-(2-phenylethoxy)-2-pyrazinyl]-2-methyl-3(2H)-pyridazinone (7 mg).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16](CC3C=CC=CC=3)[CH:10]([CH2:11][C:12](=[O:24])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[NH:16][CH:10]([CH2:11][C:12](=[O:24])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N1CC2CC(=O)CC(C1)N2Cc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC2CC(=O)CC(C1)N2
Reaction time: 48 h
Yield: 99.7 %

Procedure:
9-Benzyl-7-oxo-3,9-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (16.6 g, 50.5 mmol) was dissolved in methanol (40 mL) and added to a suspension of palladium hydroxide (1 g) in methanol (10 mL) in a Parr bottle. The Parr bottle was filled with hydrogen (40 psi) and evacuated three times. The Parr bottle was refilled with hydrogen (40 psi) and shook for 48 h. The suspension was filtered through Celite and concentrated under vacuum to give 12.1 g (quantitative yield) of 7-oxo-3,9-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester as a yellow oil. Retention time (min)=0.531, method [1], MS(ESI) 481.3 (2M+H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][NH:3][NH:2]1.[C:7](N)([CH3:10])([CH3:9])[CH3:8].C=O>>[C:7]([C:6]1[CH:5]=[CH:4][N:3]=[N:2][N:1]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: C1CNNNC1
Reactant: CC(C)(C)N
Agent: C=O
Product: CC(C)(C)c1ccnnn1
Yield: 90 %

Procedure:
In carrying out the reaction to prepare the preferred hexahydro-triazine, the tert-butylamine is added slowly to a concentrated aqueous solution of the formaldehyde (formalin) and the stoichiometry is maintained to so that there is an exact equivalent to a slight excess of the amine at the end of the reaction. Typically, a molar ratio of at least 1.00 to 1.05 of the amine to the formaldehyde is preferred for the overall process to form the tert-butyltriazine quantitatively (in excess of 90% yield). For the reaction to go to completion satisfactorily and to yield the tert-butyltriazine, careful control of the reaction conditions must be observed in order to avoid side-reactions. During the slow addition of the amine it is desirable to maintain a reaction temperature below 46° C.
Reaction SMILES: FC(F)(F)S([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])(=O)=O.[F:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([N:29]3[CH2:33][CH2:32][CH2:31][C@@H:30]3CO)=[N:27][N:28]=2)[CH:25]=1.CCN(CC)CC>CN(C=O)C>[F:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([C:26]([N:29]3[CH2:33][CH2:32][CH2:31][C@@H:30]3[O:6][Si:7]([CH:8]([CH3:9])[CH3:10])([CH:11]([CH3:12])[CH3:13])[CH:14]([CH3:15])[CH3:16])=[N:27][N:28]=2)[CH:25]=1
Reactant: OC[C@H]1CCCN1c1nnc2ccc(F)cn12
Reactant: CC(C)[Si](OS(=O)(=O)C(F)(F)F)(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)[Si](O[C@H]1CCCN1c1nnc2ccc(F)cn12)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 48.3 %

Procedure:
Triisopropylsilyl trifluoromethanesulfonate (430 mg, 1.40 mmol) was added to a solution of Intermediate 27a (220 mg, 0.93 mmol) and Et3N (190 mg, 1.86 mmol) in a DMF (2 mL) and the mixture stirred at RT for 1 h. The reaction mixture was applied to an SCX-2 cartridge (10 g) and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave the title compound (170 mg, 47%). LCMS (Method 1): Rt 4.45, m/z 393 [MH+].
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9]([NH2:14])=[N:10][C:11]=2Cl)[N:6]([C@@H:15]2[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]2[O:17][C:18](=[O:20])[CH3:19])[C:5]1=[O:33])[CH:2]=[CH2:3]>C(O)(=O)C>[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9]([NH2:14])=[N:10][CH:11]=2)[N:6]([C@@H:15]2[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]2[O:17][C:18](=[O:20])[CH3:19])[C:5]1=[O:33])[CH:2]=[CH2:3]
Reactant: C=CCn1c(=O)n([C@@H]2O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H]2OC(C)=O)c2nc(N)nc(Cl)c21
Solvent: CC(=O)O
Product: C=CCn1c(=O)n([C@@H]2O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H]2OC(C)=O)c2nc(N)ncc21
Temperature: 70 °C
Yield: 59.6 %

Procedure:
Compound 41 (0.27 g, 0.56 mmol) was dissolved in acetic acid and Zn—Cu couple was added to the solution. The mixture was heated at 70° C. for 18 h. The suspended particles were filtered off and the filtrate concentrated under vacuum. The residue was purified by flash chromatography using 10% to 100% gradient of ethyl acetate in hexanes. The solvent was removed to give 150 mg (60%) of 42 as off-white solid: 1H NMR (400 MHz, CDCl3) δ 6.05 (t, J=4.0 Hz, 1H), 6.03 (d, J=4.0 Hz, 1H), 5.87 (t, J=6.0 Hz, 1H), 5.83 (m, 1H), 5.48 (br s, 2H), 5.33 (s, 1H), 5.29 (d, J=5.6 Hz, 1H), 4.49 (d, J=3.2 Hz, 1H), 4.46 (d, J=3.2 Hz, 1H), 4.41 (d, J=5.6 Hz, 2H), 4.27 (m, 2H), 2.12 (s, 3H), 2.10 (s, 3H), 2.05 (s, 3H); MS (+)-ES [M+H]+ 450.0 m/z.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]2[O:17][CH2:16]2)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]([NH2:22])([CH3:21])([CH3:20])[CH3:19]>CO>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([OH:17])[CH2:16][NH:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2ccc(C3CO3)nc2)cc1
Reactant: CC(C)(C)N
Solvent: CO
Product: CC(C)(C)NCC(O)c1ccc(OCc2ccccc2)cn1

Procedure:
To a solution of 20.7 g. (0.091 mole) of 5-benzyloxy-2-(1,2-epoxyethyl)pyridine in 250 ml. of methanol, 25 ml. of tert-butylamine was added and the resulting solution was heated at the reflux temperature for 2.5 hours. The solvent and the excess tert-butylamine were evaporated in vacuo to give after recrystallization from hexanes, 17.3 g. (61%) of 5-benzyloxy-2-(1-hydroxy-2-tert-butylaminoethyl)pyridine; m.p. 69°-73° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:4]=1.[N:21]1([C:26]2[CH:27]=[C:28]([CH:32]=[CH:33][N:34]=2)[C:29](O)=[O:30])[CH2:25][CH2:24][CH2:23][CH2:22]1>>[Cl:14][C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:13])[C:3]([CH2:2][NH:1][C:29](=[O:30])[C:28]3[CH:32]=[CH:33][N:34]=[C:26]([N:21]4[CH2:22][CH2:23][CH2:24][CH2:25]4)[CH:27]=3)=[CH:4][N:5]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:10][CH:9]=1
Reactant: O=C(O)c1ccnc(N2CCCC2)c1
Reactant: NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O
Product: O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccnc(N2CCCC2)c1

Procedure:
N-(7-Chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-2-pyrrolidin-1-yl-iso-nicotinamide was prepared starting from intermediate D and 2-(pyrrolidin-1-yl)isonicotinic acid. MS calcd. for C26H24ClN4O2 [(M+H)+] 459.2, obsd. 459.0.
Reaction SMILES: [C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].[OH:9][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[CH:13]=[O:14].N1C=CN=C1>>[Si:5]([O:9][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[CH:13]=[O:14])([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:8])[CH3:7]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=Cc1cccc(O)c1
Agent: c1c[nH]cn1
Product: CC(C)(C)[Si](C)(C)Oc1cccc(C=O)c1

Procedure:
In a manner analogous to example 1 g, by reaction of 42.7 g (0.275 mol) of tert-butyldimethylchlorosilane with 30.5 g (0.2 mol) of 3-hydroxybenzaldehyde and (20.4 g, 0.3 mol) of imidazole. After purification on a silica column (dichloromethane 20-heptane 80), a yellow oil is obtained (m=55.9 g; Y=95%).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([O:12][CH:13]3[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=1.[O:32]1[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]1>>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([CH:35]4[CH2:36][CH2:37][O:32][CH2:33][CH2:34]4)[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=1
Reactant: O=C1CCOCC1
Reactant: Cn1c(OC2CCN(C(=O)OC(C)(C)C)CC2)nc2c(N3CCOCC3)nc(Cl)nc21
Product: Cn1c(OC2CCN(C3CCOCC3)CC2)nc2c(N3CCOCC3)nc(Cl)nc21

Procedure:
The compound was prepared from tert-butyl 4-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yloxy)piperidine-1-carboxylate following General Procedures of Boc-deprotection and reductive amination with dihydro-2H-pyran-4(3H)-one.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:17]([CH2:18][C:19]([OH:21])=O)[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=2)=[CH:5][CH:4]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:34]([NH:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH3:36]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:17]([CH2:18][C:19]([N:37]([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:35][CH3:36])=[O:21])[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=2)=[CH:7][CH:8]=1
Reactant: CCCNCCC
Reactant: COc1ccc(-c2nc3cccnc3n2CC(=O)O)cc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCN(CCC)C(=O)Cn1c(-c2ccc(OC)cc2)nc2cccnc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 32.7 %

Procedure:
Under nitrogen bubbling, a mixture of 2-(4-methoxyphenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (4.2 g, 0.015 mole) and 1,1'-carbonyldiimidazole (2.43 g, 0.015 mole) in 120 ml of tetrahydrofuran was stirred at room temperature for 3 hrs. The dipropylamine (3.04 g, 0.03 mole) was added and the reaction mixture was allowed to stir at room temperature overnight, then heated at reflux for 8 hrs. The reaction mixture was filtered and the filtrate was evaporated to dryness, then placed under high vacuum over the weekend. The residue was treated with water and the solid was collected by filtration, washed wth water, and dried under high vacuum. The solid was dissolved in 100 ml of isopropyl alcohol, filtered, and the filtrate concentrated to 50 ml. The filtrate was diluted with water, seeded, and placed in a freezer overnight. The solid was collected by filtration, washed with water, and dried under high vacuum at 50°-60° C. overnight to give 1.8 g (33%) of title compound, mp 127°-29° C.
Reaction SMILES: Cl.[NH2:2][OH:3].[C:4]([C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)(=O)[CH2:5][CH3:6].CO>O.[OH-].[Na+]>[C:4](=[N:2][OH:3])([C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)[CH2:5][CH3:6]
Reactant: CCC(=O)c1ccncc1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CCC(=NO)c1ccncc1
Yield: 75.1 %

Procedure:
To a solution of hydroxylamine hydrochloride (7 g, 0.1 mol) in H2O (40 mL) and 2N NaOH solution (50 mL) was added the compound 1 (9.46 g, 70 mmol). The reaction mixture was heated to reflux and made homogeneous by the addition of methanol (MeOH) (30 mL). After heating at reflux for 2 hours, the reaction mixture upon cooling gave the compound 2 as a white solid (7.90 g, 75%): mp 141°-144° C.; NMR (DMSO-d6) δ 1.03 (t, 3H, J=8 Hz), 2.72 (q, 2H, J=8 Hz), 3.34 (bs, 1H), 7.56 (d of d, 2H), and 8.56 (df d, 2H); IR (KBr) 1600 cm-1.
Reaction SMILES: [CH3:1]I.[Mg].[Br:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH:14]=[CH:15][N+:16]([O-:18])=[O:17].[Cl-].[NH4+]>CCOCC.O1CCCC1>[Br:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH:14]([CH3:1])[CH2:15][N+:16]([O-:18])=[O:17]
Reactant: O=[N+]([O-])C=Cc1c[nH]c2ccc(Br)cc12
Reactant: CI
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C[N+](=O)[O-])c1c[nH]c2ccc(Br)cc12
Reaction time: 12 h
Yield: 49.5 %

Procedure:
Methyl iodide (35.5 g) was added to a stirred suspension of magnesium (4.8 g) in dry ether (100 ml) over a period of 10 min. To the grey solution was added a solution of 5-bromo-3-(2-nitroethenyl)-1H-indole (13.4 g) in dry tetrahydrofuran (250 ml) over a period of 11/2 h. The resulting mass was stirred vigorously for 12 h, followed by the careful addition of saturated ammonium chloride (250 ml). After separation of the organic phase, the aqueous phase was extracted with ether (500 ml). The combined organic extracts were successively washed with 5% sodium sulphite solution (500 ml) and water (500 ml). Evaporation of the dried (MgSO4) ethereal phase gave a brown oil which was chromatographed on Kieselgel 60 using diethyl ether as eluant to give the title compound as a yellow gum (7.03 g) T.L.C. silica/diethyl ether Rf 0.5.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][NH:7][CH2:8][CH2:9][OH:10].[C:11](Cl)(=[O:23])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[OH:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][N:7]([CH2:8][CH2:9][OH:10])[C:11](=[O:23])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: OCCNCCNCCO
Reactant: CCCCCCCCCCCC(=O)Cl
Product: CCCCCCCCCCCC(=O)N(CCO)CCNCCO

Procedure:
5.3 g of N,N'-Bis(2-hydroxyethyl)ethylenediamine and 3.0 g of dodecanoyl chloride were reacted together following the procedure under Example 3. This provided 3.3 g of pure product, m.p. 94° C.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@@H:6]1Br)(=[O:3])[CH3:2].[C:25]1([S:31]([O-:34])(=[O:33])=[S:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[Na+].C(OCC)(=O)C>C(#N)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:25]1([S:31]([O:34][C@@H:6]2[O:7][C@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:5]2[O:4][C:1](=[O:3])[CH3:2])(=[O:33])=[S:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CC(=O)OC[C@H]1O[C@H](Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Reactant: O=S([O-])(=S)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@@H](OS(=O)(=S)c2ccccc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Temperature: 70 °C
Reaction time: 5 h
Yield: 67.4 %

Procedure:
2,3,4,6-Tetra-O-acetyl-α-galactopyranosyl bromide (2.0 g, 5 mmol) was dissolved in anhydrous acetonitrile (80 mL). To this sodium phenylthiosulfonate (2.02 g, 10.3 mmol) and tetrabutylammonium bromide (160 mg, 0.5 mmol) were added. The resulting mixture was stirred under argon at 70° C. After a 5 h period, t.l.c. (petrol:ethyl acetate, 1:1) indicated the formation of a product (Rf 0.4) with complete consumption of the starting material (Rf 0.6). The solution was concentrated in vacuo. The crude oil was partitioned between DCM (50 mL) and water (50 mL), and the aqueous layer re-extracted with DCM (2×50 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (petrol:ethyl acetate, 2:1) to afford the title product (1.7 g, 65%, 2 steps) as a white crystalline solid; mp 53-54° C.; [α]D27+24.2 (c, 1.0 in CHCl3); δH (400 MHz, CDCl3) 1.98, 2.03, 2.06, 2.11 (4×3H, 4×s, 4×OAc), 3.85 (1H, dd, J5,6 8.8 Hz, J6,6′ 14.0 Hz, H-6), 3.95-4.00 (2H, m, H-5, H-6), 5.11 (1H, dd, J2,3 9.7 Hz, J3,4 3.3 Hz, H-3), 5.23 (1H, at, J10.3 Hz, H-2), 5.25 (1H, d, J1,2 10.2 Hz, H-1), 5.43 (1H, dd, J3,4 3.6 Hz, J4,5 1.0 Hz, H-4), 7.54-7.68 (3H, m, Ar—H), 7.93-7.97 (2H, m, Ar—H).
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:18][C:17]2[CH:16]=[C:15]3[C:10]([O:11][C@@H:12]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]5[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=5)=[CH:21][CH:20]=4)[CH2:13][NH:14]3)=[CH:9][C:8]=2[CH2:7][N:6]1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:4].[OH-].[Li+].Cl>C1COCC1.CO>[C:38]([O:37][C:35]([N:6]1[CH:5]([C:3]([OH:4])=[O:2])[CH2:18][C:17]2[CH:16]=[C:15]3[C:10]([O:11][C@@H:12]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]5[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=5)=[CH:21][CH:20]=4)[CH2:13][NH:14]3)=[CH:9][C:8]=2[CH2:7]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]
Reactant: COC(=O)C1Cc2cc3c(cc2CN1C(=O)OC(C)(C)C)O[C@@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)CN3
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1Cc2cc3c(cc2CC1C(=O)O)NC[C@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)O3
Temperature: 25 °C
Reaction time: 4 h

Procedure:
(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester 7-methyl ester (598 mg) was dissolved in THF/methanol (4:1). 2 N Lithium hydroxide (1 mL) was added, and the resulting reaction mixture was stirred at room temperature for 4 hours. Excess 1N HCl was added and the mixture extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and the solvent was removed under reduced pressure to give the product in substantially pure form (0.56 g).