Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[CH:8]=[N:9][CH:10]=[N:11][CH:12]=1)=O.[N+]([O-])(O)=O.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=1[NH:28][C:29]([NH2:31])=[NH:30].[OH-].[Na+]>C(O)(C)C>[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=1[NH:28][C:29]1[N:31]=[C:5]([C:7]2[CH:8]=[N:9][CH:10]=[N:11][CH:12]=2)[CH:4]=[CH:3][N:30]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1NC(=N)N
Reactant: CN(C)/C=C/C(=O)c1cncnc1
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: CC(C)O
Product: Cc1ccc([N+](=O)[O-])cc1Nc1nccc(-c2cncnc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.5 %

Procedure:
(2E)-3-(Dimethylamino)-1-pyrimidin-5-ylprop-2-en-1-one (1 g, 5.6 mmol) and N-(2-methyl-5-nitrophenyl)guanidine nitrate (1.44 g, 5.6 mmol) (Z. Szakacs et al., J. Med. Chem. 2005, 48, 249) were suspended in 20 mL of isopropanol. Sodium hydroxide (0.28 g, 7 mmol) was then added. The mixture solution was stirred overnight and cooled to room temperature. The solid was collected by filtration and rinsed with isopropanol and diethyl ether. The filtrate was concentrated under reduced pressure and the residue was dissolved in 15 mL of isopropanol. The solution obtained was refluxed overnight and cooled to room temperature. The solid was collected by filtration and rinsed with isopropanol and diethyl ether. The pooled solid was rinsed with water and diethyl ether, and dried in vacuum to obtain 1.2 g (70% yield) of the title compound. MS (M+1)=309.10.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][NH:9][OH:10].N1C=CC=CC=1.[Cl:17][CH2:18][C:19]([CH3:24])([CH3:23])[C:20](Cl)=[O:21].NO>C(Cl)Cl.CCCCCC>[Cl:17][CH2:18][C:19]([CH3:24])([CH3:23])[C:20]([N:9]([CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[OH:10])=[O:21]
Reactant: CC(C)(CCl)C(=O)Cl
Reactant: ONCc1ccccc1Cl
Agent: NO
Solvent: CCCCCC
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(CCl)C(=O)N(O)Cc1ccccc1Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 20.6 %

Procedure:
Under an argon atmosphere a stirred solution of 10.2 grams (0.065 mole) of N-(2-chlorophenylmethyl)hydroxylamine and 6.1 grams (0.077 mole) of pyridine in 80 ml of methylene chloride was cooled to -10°. A solution of 10.0 grams (0.065 mole) of 3-chloro-2,2-dimethylpropionyl chloride in 20 ml of methylene chloride was added dropwise to the hydroxylamine solution during a 20 minute period. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature where it was stirred for 16 hours. The reaction mixture was diluted with 100 ml of methylene chloride and washed with 100 ml of water, 100 ml of aqueous 10% hydrochloric acid, and finally 100 ml of water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a residual oil. The oil was taken up in 25 ml of hexane and cooled in an icewater bath. The resultant solid precipitate was collected by filtration and recrystallized from hexaneethyl acetate to give 3.7 grams of 3-chloro-N-(2-chlorophenyl)methyl-N-hydroxy-2,2-dimethylpropanamide; mp 108°-110°.
Reaction SMILES: NC([N:4]1C[C:11]2[C:6](=[CH:7][CH:8]=[C:9](CN)[CH:10]=2)[CH2:5]1)=O.Br[CH2:16][C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][C:26]=1[CH2:27]Br)[C:20]([O:22][CH3:23])=[O:21].CC1C=C(C=CC=1C)C(OC)=O.C(N)C1C=CC=CC=1>>[C:6]1([CH2:5][N:4]2[CH2:16][C:17]3[C:26](=[CH:25][CH:24]=[C:19]([C:20]([O:22][CH3:23])=[O:21])[CH:18]=3)[CH2:27]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: COC(=O)c1ccc(CBr)c(CBr)c1
Reactant: NCc1ccc2c(c1)CN(C(N)=O)C2
Agent: COC(=O)c1ccc(C)c(C)c1
Solvent: NCc1ccccc1
Product: COC(=O)c1ccc2c(c1)CN(Cc1ccccc1)C2

Procedure:
The [2-(aminocarbonyl)-2,3-dihydro-1H-isoindol-5-yl]methanamine of general formula III may be prepared as follows, for example: The methyl 3,4-bis-(bromomethyl)benzoate obtainable in situ from methyl 3,4-dimethylbenzoate by photobromination, on being reacted with benzylamine, yields methyl 2,3-dihydro-2-(phenyl-methyl)-1H-isoindol-5-carboxylate, the ester function of which is converted in the usual way into a carboxamide function and then, by reduction with lithium aluminium hydride, into an aminomethyl function; the primary amino group is protected with a tert.butoxycarbonyl group, the benzyl group in the 2-position is removed by hydrogenolysis and replaced by an aminocarbonyl group, e.g. by treating the hydrochloride of the resulting 5-[[(tert.butoxycarbonyl)amino]methyl]-2,3-dihydro-1H-isoindole with sodium cyanate; removal of the tert.butoxycarbonyl protecting group, e.g. with methanolic hydrogen chloride solution, then yields the desired 2-(amino-carbonyl)-2,3-dihydro-1H-isoindol-5-yl]methanamine in the form of the hydrochloride.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[CH2:22]Br)[CH:7]=1)[CH3:2].[NH:25]1[CH2:29][CH2:28][NH:27][C:26]1=[O:30]>>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[CH2:22][N:25]2[CH2:29][CH2:28][NH:27][C:26]2=[O:30])[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CBr)c1
Reactant: O=C1NCCN1
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CN2CCNC2=O)c1

Procedure:
Prepared according to the procedure described in Example 116, Step 1, using the following starting materials: [3-(4-bromo-2-bromomethyl-phenoxy)-4-methoxy-phenyl]acetic acid ethyl ester and 2-imidazolidone.
Reaction SMILES: [C:1]1(=O)[O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:9](O)([OH:13])[CH2:10]CC.[OH-].[K+]>>[CH2:6]([OH:7])[CH2:5][CH2:4][CH2:3][OH:13].[CH2:9]([CH:5]([CH2:4][CH2:3][CH2:2][CH3:1])[CH2:6][OH:7])[CH3:10]
Reactant: O=C1CCCCCO1
Reactant: CCCC(O)O
Agent: [K+]
Agent: [OH-]
Product: CCCCC(CC)CO
Product: OCCCCO
Temperature: 80 °C

Procedure:
350.0 g (1.47 gram equivalent) of the IPDI uretdione polyisocyanate from Example 1, which had a 19.2% content of uretdione groups after hot titration, was put in first under dry nitrogen and heated to 80° C. A mixture of 176.0 g (0.88 gram equivalent) of a commercial ε-caprolactone polyesterdiol started on 1.4 butanediol, with an OH number of 280 mg KOH/g (Capa 203, produced by Solvay), 19.8 g (0.44 gram equivalent) of 1,4-butanediol and 19.5 g (0.15 gram equivalent) of 2-ethyl-1-hexanol was added within 30 minutes and agitated at a maximum reaction temperature of 100° C. until the NCO content of the mixture had dropped to a value of 0.8% after about 4 hours. The melt was poured onto a metal sheet to cool it and a polyaddition compound, containing uretdione groups and appropriate for cross-linking coating powders, was obtained in the form of a solid, colorless resin. The product had the following properties:
Reaction SMILES: C([N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]1([CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:15]#N)(=O)C1C=CC=CC=1.[Cl-:25].[Al+3].[Cl-].[Cl-].[OH-:29].[Na+]>ClCCCl>[ClH:25].[NH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]21[CH2:17][CH2:18][C:19]1[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:15]2=[O:29]
Reactant: [Cl-]
Reactant: N#CC1(CCc2ccccc2)CCCCN1C(=O)c1ccccc1
Reactant: [OH-]
Agent: [Al+3]
Agent: [Na+]
Solvent: ClCCCl
Product: Cl
Product: O=C1c2ccccc2CCC12CCCCN2

Procedure:
In 250 ml of 1,2-dichloroethane was dissolved 7.64 g of 1-benzoyl-2-(2-phenylethyl)-2-piperidinecarbonitrile. To this solution was added 8.0 g of aluminum chloride and the mixture was refluxed for 6 hours. The reaction mixture was then cooled and poured cautiously into 10% aqueous sodium hydroxide and extracted with methylene chloride and water. The methylene chloride layer was dried over anhydrous sodium sulfate and filtered and the solvent was distilled off. To the group was added 100 ml of methanol and 100 ml of 20% aqueous sodium hydroxide and the mixture was refluxed for 12 hours. After cooling, methanol was distilled off and the group was extracted with methylene chloride and water. The methylene chloride layer was dried over anhydrous sodium sulfate and filtered and the solvent was distilled off. The group was purified by alumina column chromatography using ethyl acetate-hexane (1:2) as the eluent. The active fraction was concentrated under reduced pressure and the group was treated with 6.0 ml of 4N-methanolic hydrochloric acid to give a solid. This solid was recrystallized from methylene chloride to provide 3.0 g of colorless crystals.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:13][Li]>O1CCCC1.CCOCC>[CH3:13][C:10]1[CH:11]=[CH:12][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][N:9]=1
Reactant: c1ccc(-c2cccnc2)cc1
Reactant: [Li]C
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1ccc(-c2ccccc2)cn1
Temperature: 0 °C
Reaction time: 1 h
Yield: 21.3 %

Procedure:
A solution of 3-(phenyl)pyridine (1.55 g, 10 mmol) in tetrahydrofuran (10 ml) was stirred at −78° C. and treated with methyllithium (1.4 M, 7.5 mL, 10 mmol) in ether. The resulting yellow solution was stirred for 1 h, allowed to warm to 0° C., stirred 1 h, quenched with saturated ammonium chloride, and extracted with ether. The combined organic phase was washed with water and with brine, dried (MgSO4), and concentrated in vacuo. The residue was chromatographed (silica gel, 25% ethyl acetate/hexane) to give the title compound (0.36 g).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9](I)[CH:8]=2)[C:5]2[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=2[N:3]=1.C[Sn](C)(C)[C:20]1[S:21][CH:22]=[CH:23][N:24]=1>>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:20]3[S:21][CH:22]=[CH:23][N:24]=3)[CH:8]=2)[C:5]2[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=2[N:3]=1
Reactant: C[Sn](C)(C)c1nccs1
Reactant: Nc1nc2ccccc2n1-c1cccc(I)c1
Product: Nc1nc2ccccc2n1-c1cccc(-c2nccs2)c1

Procedure:
2-Amino-1-[3(2-thiazolyl)phenyl]benzimidazole was prepared from 1-(2-amino-1-benzimidazolyl)-3-iodobenzene and 2-trimethylstannylthiazole by method C. mp 224°-226° C.
Reaction SMILES: CC1(C)CC(C[N:10]=C=O)(C)CC(N=C=O)C1.[C:17]([O:21][CH2:22][CH2:23]CCO)(=[O:20])[CH:18]=[CH2:19]>>[C:17]([OH:21])(=[O:20])[CH:18]=[CH2:19].[NH2:10][C:17]([O:21][CH2:22][CH3:23])=[O:20]
Reactant: C=CC(=O)OCCCCO
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
A urethane acrylate was prepared with IPDI, 4-hydroxybutyl acrylate, and a 4000 MW polyether diol in an equivalent ratio of 3/2/1. The reaction product was a clear, colorless liquid. At 25° C. the viscosity was 11,000 cps.
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH2:12]O)=[CH:10][C:9]2[C:4](=[C:5]([Cl:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.O=S(Cl)Cl.[N-:19]=[N+:20]=[N-:21].[Na+]>C(Cl)(Cl)Cl>[N:19]([CH2:12][C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[Cl:14])=[N+:20]=[N-:21]
Reactant: [N-]=[N+]=[N-]
Reactant: OCc1cc2cccc(Cl)c2nc1Cl
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: [N-]=[N+]=NCc1cc2cccc(Cl)c2nc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
A solution of (2,8-dichloroquinolin-3-yl)methanol (228 mg, 1 mmol) in CHCl3 (4 mL) was treated with SOCl2 (0.36 mL, 5 eq) dropwise, and the reaction was stirred at rt for 2 h before removal of solvents and the residue was partitioned between EtOAc and NaHCO3. The organic was separated and dried over Na2SO4. Solvents were removed under reduced pressure and the residue was dried under vacuum. The residue was dissolved in DMSO (2 mL) and treated with NaN3 (72 mg, 1.1 eq) at rt. LCMS showed completion after 4 h. The reaction mixture was partitioned between EtOAc (2 mL) and water (1 mL), and the water layer was extracted with EtOAc (5 mL) once and combined organics were washed with water, brine, dried over Na2SO4 and concentrated to give a pale yellow solid as 3-(azidomethyl)-2,8-dichloroquinoline (215 mg, 85%, 2 steps). This solid (50 mg, 0.2 mmol) in DCM (2 mL) was treated with piperidine (143 μL, 7.3 eq) in EtOH (2 mL) at reflux over night. The reaction was worked up and the residue was purified by column chromatography on silica gel (eluent: EtOAc/hexane, 1/5) to give a yellow solid (30 mg, 50%). 1H NMR (400 MHz, CDCl3) δ ppm 8.01 (1 H, s), 7.62 (1 H, t, J=8.0 Hz), 7.53 (1 H, d, J=8.0 Hz), 7.49 (1H, d, J=8.0 Hz), 4.02 (2H, s), 3.26-3.23 (m, 4H), 1.74-1.58 (m, 6H). Mass Spectrum (ESI) m/e=302 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21](Cl)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10].[CH:25]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)([CH3:27])[CH3:26]>>[F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([CH:25]([CH3:27])[CH3:26])[CH:33]=3)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10]
Reactant: CC(NC(=O)c1coc(Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Reactant: CC(C)c1cccc(B(O)O)c1
Product: CC(C)c1cccc(-c2nc(C(=O)NC(C)c3cc(F)c(NS(C)(=O)=O)c(F)c3)co2)c1
Yield: 16.6 %

Procedure:
2-Chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (50 mg, 0.13 mmol) was reacted with 3-isopropyl phenyl boronic acid (43 mg, 0.26 mmol) to give the title compound (10 mg, 16%) after purification by column chromatography (gradient 12% to 100% EtOAc in n-hexane).
Reaction SMILES: CS(OC[CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[N:9]([C@H:14]([C:17]([NH2:19])=[O:18])[CH2:15][CH3:16])[CH2:8]1)(=O)=O.[I-:20].[Na+].[CH2:22]1COCC1>>[I:20][CH2:22][CH:12]1[CH2:7][CH2:8][N:9]([C@@H:14]([CH2:15][CH3:16])[C:17]([NH2:19])=[O:18])[C:10](=[O:13])[CH2:11]1
Reactant: C1CCOC1
Reactant: CC[C@@H](C(N)=O)N1CC(COS(C)(=O)=O)CCC1=O
Reactant: [I-]
Agent: [Na+]
Product: CC[C@@H](C(N)=O)N1CCC(CI)CC1=O
Temperature: 0 °C
Reaction time: 5 h
Yield: 66 %

Procedure:
In a 150 ml three necked flask fitted with magnetic stirrer and reflux condenser, under inert atmosphere, 6.88 g (23.5 mmoles) of {1-[(1S)-1-(aminocarbonyl)propyl]-6-oxo-3-piperidinyl}methyl methanesulfonate 24 were dissolved in 86 ml of THF. 3.9 g (25.9 mmoles, 1.1 eq) of sodium iodide were added in one portion and the mixture was brought to reflux. After 5 hours, 780 mg (5.2 mmoles, 0.22 eq) of sodium iodide were added and reflux continued for a total of 10 hours. After cooling down to 0° C., the mixture was filtered, the precipitate washed with THF, the combined organic fractions concentrated to dryness and purified by PrepLC (800 g SiO2, CH2Cl2/MeOH, 95/5) to give 7.21 g of crude compound. It was crystallised from 80 ml ethanol to give 5 g of pure iodide 13, 66% yield.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]2[CH2:15][O:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:16]=[N+:17]=[N-:18].[Na+].[Cl-].[NH4+]>CO.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]([OH:14])[CH2:15][N:16]=[N+:17]=[N-:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CC[C@H]([C@H]2CO2)C1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CC[C@H]([C@H](O)CN=[N+]=[N-])C1
Yield: 103.5 %

Procedure:
A solution of (S)—(S)-3-oxiranylpyrrolidine-1-carboxylic acid t-butyl ester (1.1 g, 4.9 mmol, 1.0 eq.), sodium azide (800 mg, 12.3 mmol, 2.5 eq.), and ammonium chloride (474 mg, 8.9 mmol) in MeOH (25 mL) was stirred at reflux overnight. The white solid residue obtained on removal of solvent was dissolved in EtOAc (25 mL) and washed with water and saturated aqueous NaCl (1×25 mL each). The organic layer was then dried over Na2SO4 and concentrated to yield (S)-3-((S)-2-azido-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (1.3 g).
Reaction SMILES: [C:1]([NH2:4])(=[NH:3])[CH3:2].[Cl:5][C:6]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:7]=1[CH:8]=[CH:9][S:10](Cl)(=[O:12])=[O:11]>>[Cl:5][C:6]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:7]=1[CH:8]=[CH:9][S:10]([N:3]=[C:1]([NH2:4])[CH3:2])(=[O:12])=[O:11]
Reactant: O=S(=O)(Cl)C=Cc1c(Cl)cccc1Cl
Reactant: CC(=N)N
Product: CC(N)=NS(=O)(=O)C=Cc1c(Cl)cccc1Cl

Procedure:
Reaction of acetamidine with 2,6-dichlorostyrylsulfonyl chloride according to the procedure of Example 29(b) affords N'-[(2,6-dichlorostyryl)sulfonyl]acetamidine, m.p. 154.5°-158.5° C. (corr.), from absolute ethanol.
Reaction SMILES: [CH2:1]([N:12]1[C:21](=[O:22])[C:20]2[N:19]([CH3:23])[CH:18]=[N:17][C:16]=2[N:15]([CH3:24])[C:13]1=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]CC=C.C[N+]1([O-])CC[O:29]CC1.S([O-])([O-])=O.[Na+].[Na+].[CH3:39][C:40]([CH3:42])=[O:41]>O>[OH:41][CH:40]([CH2:42][OH:29])[CH2:39][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][N:12]1[C:21](=[O:22])[C:20]2[N:19]([CH3:23])[CH:18]=[N:17][C:16]=2[N:15]([CH3:24])[C:13]1=[O:14]
Reactant: CC(C)=O
Reactant: C=CCCCCCCCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Reactant: C[N+]1([O-])CCOCC1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Product: Cn1cnc2c1c(=O)n(CCCCCCCCCC(O)CO)c(=O)n2C
Reaction time: 6 h
Yield: 76 %

Procedure:
A solution of 1-(10-undecenyl)-3,7-dimethylxanthine, prepared above (4.3 g, 13 mmol), 4-methylmorpholine-N-oxide (1.942 g, 16.6 mmol) and potassium osmate dihydrate (9.5 mg; 0.026 mmol) in acetone (45 ml) and water (10 ml) was stirred for 6 hours. A solution of 20% aqueous sodium sulphite (12 ml) was added and stirred for 30 minutes. The reaction mixture was extracted with 25% ethanol/dichloromethane (4×100 ml). The combined organic extracts were dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by flash chromatography over silica gel using a methanol/5% dichloromethane eluent to obtain 3.6 g of 1-(10,11-dihydroxyundecanyl)-3,7-dimethylxanthine (yield, 76%).
Reaction SMILES: [C:1]([C:5]1[C:6]([O:35][CH3:36])=[C:7]([CH:24]=[C:25]([N:27]2[CH:32]=[CH:31][C:30](=[O:33])[NH:29][C:28]2=[O:34])[CH:26]=1)/[CH:8]=[CH:9]/[C:10]1[CH:18]=[CH:17][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])=[CH:15][C:11]=1[C:12](Cl)=[O:13])([CH3:4])([CH3:3])[CH3:2].[H-].C(O[Al+2])(C)(C)C.[Li+].[H-].[H-]>C1COCC1>[C:1]([C:5]1[C:6]([O:35][CH3:36])=[C:7]([CH:24]=[C:25]([N:27]2[CH:32]=[CH:31][C:30](=[O:33])[NH:29][C:28]2=[O:34])[CH:26]=1)/[CH:8]=[CH:9]/[C:10]1[CH:18]=[CH:17][C:16]([NH:19][S:20]([CH3:23])(=[O:21])=[O:22])=[CH:15][C:11]=1[CH2:12][OH:13])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1c(/C=C/c2ccc(NS(C)(=O)=O)cc2C(=O)Cl)cc(-n2ccc(=O)[nH]c2=O)cc1C(C)(C)C
Agent: CC(C)(C)O[Al+2]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1c(/C=C/c2ccc(NS(C)(=O)=O)cc2CO)cc(-n2ccc(=O)[nH]c2=O)cc1C(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
To a solution of the product from Example 126, Part A (375 mg, 0.705 mmol) in anhydrous THF (5 ml) at 0° C. under N2 gas was added a 1.0 M solution of lithium tert-butoxyaluminiumhydride (1.8 ml, 1.8 mmol) dropwise. The resulting mixture was stirred at 0° C. for 30 min, and then allowed to warm to room temperature and was stirred for 1 h. The mixture was partitioned between 1 N aq. HCl (10 ml) and EtOAc (2×10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using 3% MeOH in CH2Cl2 as the eluent to give the title compound (220 mg, 63%). 1H NMR (300 MHz, DMSO-d6) δ ppm 11.41 (s, 1H) 9.82 (s, 1H) 7.73 (t, J=8.27 Hz, 2H) 7.66 (d, J=2.57 Hz, 1H) 7.31-7.39 (m, 2H) 7.20 (d, J=2.57 Hz, 1H) 7.12-7.19 (m, 2H) 5.65 (d, J=8.09 Hz, 1H) 5.28 (t, J=5.52 Hz, 1H) 4.65 (d, J=5.52 Hz, 2H) 3.79 (s, 3H) 3.00 (s, 3H) 1.38 (s, 9H).
Reaction SMILES: C(ON)C.[CH2:5]([O:7][C:8](=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1F)[CH3:6].[S-2:18].[Na+].[Na+]>CN(C=O)C.C(OCC)(=O)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH2:5]([O:7][C:8](=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[SH:18])[CH3:6]
Reactant: [S-2]
Reactant: CCOC(=O)c1cccc(F)c1F
Agent: CCON
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cccc(F)c1S
Reaction time: 10 h

Procedure:
Example 37(a) was prepared in a similar manner to that described for Example 35(a) except that the starting material described below was employed and that ethoxyamine was used instead of propylamine: 1H NMR (300 MHz, CDCl3) δ 8.59 (m, 1H), 8.08 (d, 1H), 7.88 (d, 1H, J=16.4 Hz), 7.79 (t, 1H), 7.65 (d, 1H), 7.60 (m, 1H), 7.50 (d, 1H, J=16.4 Hz), 7.40 (t, 1H), 7.36 (d, 1H), 7.28 (s, 1H), 7.23 (m, 1H), 7.10 (d, 1H), 3.90 (q, 2H), 1.19 (t, 3H). LCMS (100% area) Rt=4.85 min, (pos) [M+H]/z Calc'd 435.1, found 435.1, (neg) [M−H]/z Calc'd 433.1, found 433.1. Analyzed with 0.35H2O, 0.07 EtOAc Calc'd, C (62.56), H (4.57), N (12.54), S (7.17). Found: C (62.61), H (4.55), N (12.49), S (7.11). Starting material was prepared as follows: A solution of ethyl-2,3 difluorobenzoate (1.07 g, 5.75 mmol) in DMF (10 mL) was treated with sodium sulfide (896 mg, 11.5 mmol, 2.0 equiv) at 23° C. The mixture was stirred under argon for 10 h. The solution was diluted with ethyl acetate (50 mL) and water (50 mL) and 10% citric acid (5 mL). The organic layer was washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, decanted and concentrated under reduced pressure to give 3-Fluoro-2-mercapto-benzoic acid ethyl ester. 1H NMR (300 MHz, CDCl3)57.71 (t, 1H), 7.38 (m, H), 7.12 (m, 1H), 4.41 (q, 2H), 1.40 (t, 3H); LCMS (100% area) Rt=4.53 min, (pos) [M+H]/z Calc'd 201.0, found 200.9.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5](=O)[NH:6][CH:7]=1.N1C=CC=CC=1.P(Cl)(Cl)([Cl:20])=O.C(=O)([O-])[O-].[Na+].[Na+]>ClC1C=CC=CC=1>[Cl:20][C:5]1[C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1c[nH]c(=O)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Clc1ccccc1
Solvent: c1ccncc1
Product: Cc1cnc(Cl)c([N+](=O)[O-])c1
Yield: 75.3 %

Procedure:
A solution of 5-methyl-3-nitro-1H-pyridone (3.1 g, 20 mmol) in 50 mL chlorobenzene was treated with pyridine (0.47 g, 6.0 mmol) and phosphorus oxychloride (4.7 g, 30.8 mmol). The mixture was refluxed for 1 h. Upon cooling it was treated with sodium carbonate aq. followed by extraction with CH2Cl2. The organic phase was dried over Mg2SO4 and filtered. The solvent was evaporated in vacuo to give 2.6 g of the titled compound which was further purified by flash chromatography on silica gel (PE:EtOAc, 8:2, v/v). 1H-NMR (CDCl3) δ: 2.45 (s, 3H, CH3), 8.44 (d, 1H, J=2.0 Hz, Py-H), 8.58 (d, 1H, J=2.0 Hz, Py-H); MS (ESI+) m/z 173.0209 [M+H]+, C6H5ClN2O2 requires 172.0040.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3C(=CC=CC=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9].C(C1C(N[C@H]2[C@@H](O)C[N:36]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])C2)=NC(CC)=CN=1)C>>[Br:1][C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@H:11]2[C@@H:12]([OH:20])[CH2:13][N:36]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[CH2:19]2)=[N:6][C:7]=1[CH2:8][CH3:9]
Reactant: CCc1cnc(CC)c(N[C@@H]2CN(C(=O)OCc3ccccc3)C[C@@H]2O)n1
Reactant: CCc1nc(N[C@@H]2c3ccccc3C[C@@H]2O)c(CC)nc1Br
Product: CCc1nc(N[C@@H]2CN(C(=O)OCc3ccccc3)C[C@@H]2O)c(CC)nc1Br

Procedure:
Following the procedure for the preparation of (1R,2S)-1-[(5-bromo-3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol but substituting benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-hydroxypyrrolidine-1-carboxylate and making non-critical variations provided the title compound as a oil: 1H NMR (400 MHz, CDCl3) δ) 7.38, 5.16, 4.91, 4.82, 4.59, 4.48, 4.59, 4.48, 4.01, 3.72-3.58, 3.36-3.25, 2.81, 2.69, 2.54, 2.46, 1.31-1.23.