Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6](=[O:33])[C@H:7]([N:11]([CH2:23][C:24]1[CH:32]=[CH:31][C:27]2[N:28]=[CH:29][NH:30][C:26]=2[CH:25]=1)[S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])(C)(C)C.FC(F)(F)C(O)=O.C(Cl)Cl>>[N:28]1[C:27]2[CH:31]=[CH:32][C:24]([CH2:23][N:11]([S:12]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)(=[O:14])=[O:13])[C@H:7]([CH:8]([CH3:10])[CH3:9])[C:6]([OH:33])=[O:5])=[CH:25][C:26]=2[NH:30][CH:29]=1
Reactant: COc1ccc(S(=O)(=O)N(Cc2ccc3nc[nH]c3c2)[C@@H](C(=O)OC(C)(C)C)C(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)N(Cc2ccc3nc[nH]c3c2)[C@@H](C(=O)O)C(C)C)cc1
Yield: 86.5 %

Procedure:
A solution of 2(R)-[(benzimidazol-5-ylmethyl)-(4-methoxybenzenesulfonyl)amino]-3-methylbutyric acid tert-butyl ester (74 mg, 0.156 mmol) in a 1:4 trifluoroacetic acid/methylene chloride mixture (5 mL) was stirred for 2 h. The reaction mixture was concentrated on a roto-evaporator and then on high-vac pump to give 2(R)-[(benzimidazol-5-ylmethyl)-(4-methoxybenzenesulfonyl)amino]-3-methylbutyric acid (approx. 0.135 mmol).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[N:8][C:9]([N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])=[N:10][C:11]=1[CH:12]([CH3:14])[CH3:13])=O)C.[H-].C([Al+]CC(C)C)C(C)C.O>C1(C)C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:7]2[C:6]([CH2:4][OH:3])=[C:11]([CH:12]([CH3:14])[CH3:13])[N:10]=[C:9]([N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])[N:8]=2)=[CH:22][CH:23]=1
Reactant: CCOC(=O)c1c(-c2ccc(F)cc2)nc(N(C)S(C)(=O)=O)nc1C(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1CO
Temperature: -78 °C
Reaction time: 1 h
Yield: 80.9 %

Procedure:
Ethyl 2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-carboxylic acid (100.0 g) and toluene (500.0 mL) were added to a reactor under nitrogen atmosphere. The reaction mixture was cooled to −78° C. A solution of diisobutylaluminium hydride in toluene (1.5 M, 200.0 mL) was slowly added thereto. The temperature of the reaction mixture was adjusted to 0° C. The reaction mixture was stirred for over 1 hour and then water (500.0 mL) was added thereto. The separated organic layer was sequentially washed with 1N hydrochloric acid solution (500.0 mL), 5% sodium bicarbonate solution (500.0 mL), and then water (500.0 mL), and then concentrated under reduced pressure. n-Hexane (300.0 mL) was added to the resulting residue under stirring. The resulting suspension was filtered under reduced pressure, and then dried to obtain N-[4-(4-fluorophenyl)-5-hydroxymethyl-6-isopropyl-pyrimidin-2-yl]-N-methyl-methanesulfonamide as a white solid (72.3 g, yield 81%).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]([CH:16]2[CH2:18][CH2:17]2)C(=O)OC(C)(C)C)[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1.[Cl:24][C:25]1[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>O.CN1C(=O)CCC1>[Cl:24][C:25]1[CH:26]=[C:27]([CH:28]=[CH:29][CH:30]=1)[O:31][C:2]1[CH:7]=[C:6]([NH:8][CH:16]2[CH2:17][CH2:18]2)[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1
Reactant: Oc1cccc(Cl)c1
Reactant: CC(C)(C)OC(=O)N(c1cc(Cl)nc2c(C=O)cnn12)C1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=Cc1cnn2c(NC3CC3)cc(Oc3cccc(Cl)c3)nc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (1.0 eq, 49 mg, 0.145 mmol) was mixed in a vial with NMP (0.2 ml), 3-chlorophenol (5.0 eq, 93 mg, 0.274 mmol) and potassium carbonate (5.0 eq, 100 mg, 0.723 mmol). The reaction mixture was stirred at room temperature for one hour. Water was added and the resulting gummy material was extracted with methylene chloride. The organic phase was dried over Na2SO4 and the volatiles removed in vacuo. The resulting NMP solution was reacted with a HCl 4N solution in dioxane (5 ml) at room temperature for one hour, at which time LCMS monitoring indicated completion of the reaction. The reaction was treated with water and 6N NaOH and stirred overnight at room temperature. The solid was filtered and dried to afford crude 5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde as a solid (31 mg). The material was heated with hydantoin (30 mg), piperidine (30 uL) in Ethanol (1 ml) in a vial at 90° C. for seven hours. Water was added and the material was filtered, washed with ethanol, ethanol/water and dried. (Z)-5-((5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)imidazolidine-2,4-dione was isolated as solid (43 mg, 38% over 2 steps).). LCMS (ES):>95% pure, m/z 411 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C:5](=O)[C:4]=2[CH:3]=1.[CH3:18][Mg]Br.CCOCC.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C:5](=[CH2:18])[C:4]=2[CH:3]=1
Reactant: O=c1c2cc(Br)ccc2oc2ccc(I)cc12
Reactant: C[Mg]Br
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: ClCCl
Product: C=C1c2cc(Br)ccc2Oc2ccc(I)cc21
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A 500 ml RB flask was charged with 2-bromo-7-iodo-9H-xanthen-9-one (16.030 g, 40.0 mmol) and THF (150 mL). The mixture was stirred for 10 min at RT and the resulting suspension was placed in water-ice bath for another 10 min. Methylmagnesium bromide, 3.0 M in Et2O (20.0 ml, 60.0 mmol) was added dropwise. After 1 hr, the mixture was carefully quenched with sat NH4Cl (150 mL) at 0° C. and diluted with EtOAc. The organic layer was washed with brine, dried with sodium sulfate, and concentrated in vacuo. The material was dissolved in 100 mL of methylene chloride, treated with PPTS (0.201 g, 0.800 mmol), and heated to reflux for 2 hr. The mixture was cooled to RT, diluted with DCM, and washed with saturated sodium bicarbonate and brine. The organic fraction was dried over sodium sulfate and concentrated in vacuo to afford crude 2-bromo-7-iodo-9-methylene-9H-xanthene as a light orange solid that was advanced without further purification. MS: MH+=399.0/401.0.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([CH3:27])([CH3:26])[C:21](OCC)=[O:22])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.[OH-].[Na+]>C(OCC)(=O)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:15][CH2:16][N:17]([C:20]([CH3:27])([CH3:26])[CH2:21][OH:22])[CH2:18][CH2:19]2)=[CH:12][CH:13]=1
Reactant: CCOC(=O)C(C)(C)N1CCN(c2ccc(F)cc2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Product: CC(C)(CO)N1CCN(c2ccc(F)cc2)CC1
Reaction time: 16 h
Yield: 87.6 %

Procedure:
To a stirred solution of lithium aluminium hydride (0.774 g, 20.4 mmol) in tetrahudrofuran (20 mL) was added ethyl 2-(4-(4-fluorophenyl)piperazin-1-yl)-2-methylpropanoate (prepared according to procedure reported in Bioorganic & Medical Chemistry, 2006, 14, 2725; 2.0 g, 6.79 mmol) in tetrahudrofuran (10 mL) was added slowly at 25° C. The resulting mixture was then stirred for 16 h. After completion of reaction, ethyl acetate (5 ml) was added followed by 1N Sodium hydroxide (20 ml) and allowed to stirred for 1 h. It was then passed through a celite bed and washed with ethyl acetate (100 ml. To the filtrate water (50 ml) was added and extracted with ethyl acetate (3×50 mL), combined organic layers was dried over sodium sulphate and concentrated to afford crude product. Crude product was purified by using silica gel (100-200 mesh) column chromatography using 5% methanol in dichloromethane as eluent to obtain the titled compound (1.5 g, 87.0%).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]([CH3:13])[C:7]2[O:8][CH2:9][O:10][C:6]=2[C:5]=1[CH3:14])([O-])=O.[H][H]>[Pd].C(O)C>[NH2:1][C:4]1[CH:12]=[C:11]([CH3:13])[C:7]2[O:8][CH2:9][O:10][C:6]=2[C:5]=1[CH3:14]
Reactant: Cc1cc([N+](=O)[O-])c(C)c2c1OCO2
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Cc1cc(N)c(C)c2c1OCO2
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 99.9 %

Procedure:
A mixture of 1.88 g of 5-nitro-4,7-dimethyl-1,3-benzodioxole and 0.19 g of 10% palladium on carbon in 200 mL of ethanol is placed under a 50 psi hydrogen atmosphere. The mixture is shaken for 90 minutes at room temperature. The reaction mixture is filtered through Celite to yield a brownish solution. Concentration under reduced pressure affords 1.59 g of 5-amino-4,7-dimethyl-1,3-benzodioxole.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:13][C:12]([NH2:14])=[N:11][N:10]=1.C([O-])([O-])=O.[K+].[K+].Br.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>C(#N)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:13][C:12]([NH:14][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[N:11][N:10]=1
Reactant: Cc1ccc(-c2nnc(N)o2)c(C)c1
Reactant: BrCc1ccccn1
Agent: Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1ccc(-c2nnc(NCc3ccccn3)o2)c(C)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 97 %

Procedure:
To a solution of 5-(2,4-dimethylphenyl)-1,3,4-oxadiazol-2-amine (Example 16a) (94.5 mg, 0.5 mmol) in 5 ml of dry acetonitrile was added K2CO3 (207 mg, 1.5 mmol). To the suspension was added 2-(bromomethyl)pyridine hydrobromide (127 mg, 0.5 mmol) and the mixture was stirred at 90° C. overnight. The solvent was removed under vacuum and the solid was dissolved in EtOAc, washed successively with aq. NaHCO3 and brine, dried over MgSO4 filtered and evaporated. The residue was purified on silica gel to give 5-(2,4-Dimethylphenyl)-N-(pyridin-2-ylmethyl)-1,3,4-oxadiazol-2-amine (136 mg, 97%) as a white solid. 1H NMR (300 MHz, CdCl3): δ 2.34 (s, 3H), 2.5 (s, 3H), 5.1 (s, 2H), 7.07-7.08 (m, 2H), 7.21-7.33 (m, 2H), 7.64-7.68 (m, 2H), 8.59-8.60 (d, 1H); MS (M+H, 281).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:32]#[N:33])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH2:29][CH3:30])[CH2:28][O:27][CH2:26]3)[C:17]([O:19]C(C)(C)C)=[O:18])[C:10](=[O:31])[CH:9]=2)[CH:7]=1.[OH-].[Li+]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:32]#[N:33])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH2:29][CH3:30])[CH2:28][O:27][CH2:26]3)[C:17]([OH:19])=[O:18])[C:10](=[O:31])[CH:9]=2)[CH:7]=1
Reactant: CCC1(CC(C(=O)OC(C)(C)C)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)COC1
Agent: [Li+]
Agent: [OH-]
Product: CCC1(CC(C(=O)O)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)COC1

Procedure:
275 mg (599 μmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-ethyloxetan-3-yl)propanoate (racemate) and 3 ml of aqueous lithium hydroxide solution (1N) were reacted according to General Method 6B, giving the title compound. Yield: 193 mg (76% of theory)
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].[CH3:8][C:9]([Si:12](Cl)([CH3:14])[CH3:13])([CH3:11])[CH3:10].N1C=CN=C1.O>C1COCC1>[C:9]([Si:12]([O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6])([CH3:14])[CH3:13])([CH3:11])([CH3:10])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C=CCCCCO
Agent: c1c[nH]cn1
Solvent: C1CCOC1
Solvent: O
Product: C=CCCCCO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 104.5 %

Procedure:
To a solution of 5-hexen-1-ol (5 g, 50 mmol) in THF (80 mL) were sequentially added TBDMSCl (8.4 g, 55 mmol) and imidazole (4.01 g, 60 mmol). The mixture was stirred at rt overnight. Water was added and the two phases separated. The aq. phase was extracted with ether and the combined org. layers were dried over MgSO4 and concentrated to give the title intermediate as a colourless liquid (11.2 g, 100% yield).
Reaction SMILES: [C:1]1(=[O:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1.N.[Cl-].[NH4+].[CH2:20](OCC)C>>[CH3:20][CH:14]1[CH2:15][C:1](=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: O=C1C=CCCCCCCCCCCCC1
Reactant: CCOCC
Agent: N
Agent: O=C1/C=C/CCCCCCCCCCCC1
Agent: [Cl-]
Product: CC1CCCCCCCCCCCCC(=O)C1

Procedure:
In 10 ml of dried diethyl ether was dissolved 5 mmol of (E)-2-cyclopentadecenone, and the solution was added dropwise to the above solution at -78° C. The mixture was allowed to react at that temperature for 15 hours, and 12 ml of a 1:1 (by volume) mixture of aqueous ammonia and a saturated ammonium chloride aqueous solution was added thereto. The reaction mixture was extracted with diethyl ether, and the extracted product was purified by silica gel column chromatography using hexane/ethyl acetate (45:1 by volume) to obtain muscone in a chemical yield of 57 mol %. The resulting muscone was R-form having an optical rotation of -11.6° (at 21° C., c 5.03, MeOH) and an optical purity of 99%ee.
Reaction SMILES: [C:1]([N:5]1[C:9]([NH2:10])=[CH:8][C:7]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[C:15](OC)(=[O:20])[CH2:16][C:17]([CH3:19])=O>C(O)(=O)C>[C:1]([N:5]1[C:9]2[NH:10][C:15](=[O:20])[CH:16]=[C:17]([CH3:19])[C:8]=2[C:7]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[N:6]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)CC(C)=O
Reactant: CC(C)(C)n1nc(C2CCC2)cc1N
Solvent: CC(=O)O
Product: Cc1cc(=O)[nH]c2c1c(C1CCC1)nn2C(C)(C)C
Temperature: 105 °C
Reaction time: 19 h
Yield: 10.4 %

Procedure:
To 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (5.0 g, 25.9 mmol) in acetic acid (25 mL) was added methyl acetoacetate (5.5 mL, 51.8 mmol), and the reaction was heated to 105° C. After 19 hr, the reaction mixture was cooled to room temperature, concentrated to a viscous oil, and then taken up in EtOAc. The reaction mixture was quenched by the slow addition of an aqueous solution of NaHCO3. The layers were separated and the organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by trituration with hexanes to give, after two crops, the title compound (0.7 g, 52% yield) as a colorless solid. 400 MHz 1H NMR (CD3OD) d 6.09 (s, 1H), 3.83 (dddd, J=8.3, 8.3, 8.3, 8.3 Hz, 1H), 2.50-2.27 (m, 7H), 2.08-2.01 (m, 1H), 1.99-1.85 (m, 1H), 1.71 (s, 9H). LRMS m/z (APCI+) 260 (M+1).
Reaction SMILES: [CH3:1][C:2](=O)[CH2:3][CH2:4][C:5](=O)[CH3:6].[NH2:9][CH2:10][CH2:11][CH2:12][OH:13]>[Pd].C(O)C>[OH:13][CH2:12][CH2:11][CH2:10][N:9]1[CH:2]([CH3:1])[CH2:3][CH2:4][CH:5]1[CH3:6]
Reactant: NCCCO
Reactant: CC(=O)CCC(C)=O
Agent: [Pd]
Solvent: CCO
Product: CC1CCC(C)N1CCCO
Reaction time: 3 h
Yield: 36 %

Procedure:
A total of 3 moles of 2,5-hexanedione, 3 moles of 3-amino-1propanol, 10 g of 10% Pd/C, and 500 ml of ethanol were charged to an autoclave. The reaction mixture was pressured up to 1100 psi of H2 and kept for 3 hours at 100° C. Distillation yielded 170 g of N-(3-hydroxypropyl)-2,5-dimethylpyrrolidine (b.p.=119° C. at 25 mm).
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:15]#[N:16])[CH:11]=2)[CH:6]=1)=O.[Li+].[OH-].S(Cl)([Cl:21])=O>C1COCC1>[C:15]([C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([C:3]([Cl:21])=[O:2])[CH:14]=[CH:13]2)#[N:16]
Reactant: O=S(Cl)Cl
Reactant: COC(=O)c1ccc2cc(C#N)ccc2c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: N#Cc1ccc2cc(C(=O)Cl)ccc2c1

Procedure:
Compounds of formula II, where T is a bond, B is H, each of-e and g is C—H, f is a bond, V is a substituted carbonyl group, and Z′ is NH can be prepared as follows. Hydrolysis of naphthalene-2,6 dicarboxylic acid dimethyl ester with one equivalent of a base such as KOH, followed by acidification of the product with an acid such as HCl, affords the naphthalene mono carboxylic acid. After conversion of the carboxylic acid to an acid chloride with a reagent such as thionyl chloride and subsequent reaction with ammonia in methylene chloride, the resulting 6-carbamoyl-naphthalene-2-carboxylic acid methyl ester is reacted with triphosgene in trimethylphosphate to provide 6-cyano-naphthalene-2-carboxylic acid methyl ester. Hydrolysis of the ester with LiOH in aqueous THF solution, followed by reaction with thionyl chloride, affords 6-cyano-naphthalene-2-carbonyl chloride, which can then be coupled with alcohols or amines to provide compounds of the formula XX. The amidine, hydroxyamidine, or aminoamidine groups can be obtained from the nitrile as described previously to afford compounds the formula XXI, where R19 is H, and R22 is H, alkyl, OH, or NH2, and V is an alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, aralkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, alkoxycarbonyl, cycloalkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, or heteroaralkyloxycarbonyl.
Reaction SMILES: [Cl:1][C:2]1[C:22]([Cl:23])=[CH:21][C:5]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:7](OC(C)C)=[N:8][C:4]=2[CH:3]=1.[CH:24]1([NH2:27])[CH2:26][CH2:25]1>C1COCC1>[CH:24]1([NH:27][C:7]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:5]3[CH:21]=[C:22]([Cl:23])[C:2]([Cl:1])=[CH:3][C:4]=3[N:8]=2)[CH2:26][CH2:25]1
Reactant: CC(C)Oc1nc2cc(Cl)c(Cl)cc2n1[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Reactant: NC1CC1
Solvent: C1CCOC1
Product: C[C@H]1O[C@@H](n2c(NC3CC3)nc3cc(Cl)c(Cl)cc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 432 h
Yield: 82.6 %

Procedure:
A mixture of 5 (0.422 g, 1 mmol) and cyclopropylamine (0.694 mL, 10 mmol) in THF (10 mL) was stirred at room temperature for 18 days (with the addition of 0.694 mL of fresh cyclopropylamine on the 9th day). Volatile materials were removed by evaporation and the residue was treated with NH3/MeOH (15 mL, sat. at 0° C.) at room temperature for 18 h. The reaction mixture was again evaporated and the residue was chromatographed on a silica column (2×15 cm, eluted successively with CHCl3, 4%, 8% MeOH/CHCL3, v/v). Evaporation of fractions 23˜35 (15 mL per fraction) and recrystallization from MeCN gave 0.296 g (83%) of 6 as white crystals. MP: ˜210° C. (dec). HRMS: (EI, with DCI probe) m/z 357.0645 (51%, M+=357.0647). 1H NMR (DMSO-d-6): δ7.48 (s, 1, 4-H), 7.35 (s,1,7-H), 7.14 (d, 1,2′-NH—, J2′NH-1Cp=2 Hz), 5.62 (d, 1,1′-H, J1′-2′=6.5 Hz), 5.26 (d, 1,3′-OH, J3′-3′OH=4.5 Hz), 5.23 (d,1, 2′-OH, J2′-2′OH′=7.0 Hz),4.33 (m, 1,2′-H, J2′-3′=5.5 Hz), 3.90 (m, 1,4′H, J4′-3′=4.5 Hz, J4′-5′=6.5 hz), 3.79 (m, 1, 3′-HO, 2.76 (m, 1,1,-Cp), 1.37 (d, 3,5′-H), 0.71, 0.53 (2×m, 4, 2-Cp and 3-Cp). 13C NMR (DMSO-d-6): δ156.68 (C2), 143.53 (C3a), 132.05 (C7a), 123.27, 120.22 (C5 and C6), 116.38 (C4), 111.05 (C7), 87.56 (C1′), 80.00 (C4′), 73.65 (C3′), 70.85 (C2′), 25.17 (1-Cp), 18.93 (C5″) 6.49, 6.15 (2-Cp and 3-Cp). Anal. Calcd. for C15H17Cl2N3O3: C, 50.29, H, 4.78, N, 11.73. Found C, 50.42, H, 5.00, N, 11.99.
Reaction SMILES: [CH2:1]1[O:8][C@@H:7]2[O:9][C@H:2]1[CH:3]=[CH:4][C:5]2=[O:6].C(O)(=[O:12])C>Cl>[CH2:1]1[O:8][C@@H:7]2[O:9][C@H:2]1[CH:3]=[CH:4][C:5]2=[O:6].[C@@H:7]12[O:8][CH2:1][C@@H:2]([O:9]1)[C@@H:3]([OH:12])[CH2:4][C:5]2=[O:6]
Reactant: CC(=O)O
Agent: Cl
Agent: O=C1C=C[C@H]2CO[C@@H]1O2
Product: O=C1C[C@H](O)[C@H]2CO[C@@H]1O2

Procedure:
Levoglucosenone, an isomer of HMF, can be produced from woody (lignocellulosic) material through pyrolysis. F. Shafizadeh et al. (Carbohydrate Research, 71, (1979), 169-191) found that heating levoglucosenone in 0.5 M HCl (pH=0.3) in a boiling water bath to reaction completion (2.5 hours) produced HMF in a 16% yield. Heating levoglucosenone in 2 M acetic acid (pH=2.2) produced 1,6-anhydro-3-deoxy-β-D-erythro-hexopyranos-2-ulose, (represented by Formula (I-a)) in a 77% yield, but no HMF.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][NH2:5].[C:6](N1C(=O)CCC1=O)([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].O.C(Cl)(Cl)Cl>O1CCOCC1>[CH3:1][NH:2][CH2:3][CH2:4][NH:5][C:6](=[O:7])[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C1CCC(=O)N1C(=O)OCc1ccccc1
Reactant: CNCCN
Solvent: O
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Product: CNCCNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 96 h
Yield: 4.3 %

Procedure:
N-Methylethylenediamine (2.0 g) was dissolved in dioxane (20 ml), the solution was added with N-carbobenzoxysuccinimide (8.07 g), and the mixture was stirred at room temperature for 4 days. The reaction mixture was added with distilled water and chloroform, the layers were separated, and the organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 2:1), and then purified again by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=30:1:0.1) to obtain the title compound (243 mg).
Reaction SMILES: Br.[Br:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH2:9]([O:16][C:17](ON1C(=O)CCC1=O)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.O>O1CCCC1>[Br:2][CH:3]1[CH2:8][CH2:7][N:6]([C:17]([O:16][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:18])[CH2:5][CH2:4]1
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Reactant: BrC1CCNCC1
Agent: Br
Solvent: C1CCOC1
Solvent: O
Solvent: CN1CCOCC1
Product: O=C(OCc1ccccc1)N1CCC(Br)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.4 %

Procedure:
To a solution of 4-bromopiperidine hydrobromide (3.0 g, 12.2 mmol) in tetrahydrofuran (30 ml) were added 1-{[(benzyloxy)carbonyl]oxy}-2,5-pyrrolidinedione (3.20 g, 12.9 mmol), N-methylmorpholine (1.62 ml, 14.7 mmol) and 4-N,N-dimethylaminopyridine (30 mg) at room temperature, and stirred at room temperature for 16 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a 1N-aqueous hydrochloric acid solution, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=1/1) to obtain benzyl 4-bromo-1-piperidinecarboxylate (3.58 g, 98%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([NH:15][NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2.CCN(CC)CC.Cl[C:37]([O:39][CH3:40])=[O:38]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([NH:15][N:16]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:37]([O:39][CH3:40])=[O:38])=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: COc1c(-c2ccccc2)nc2ccccc2c1C(=O)NNc1ccccc1
Reactant: COC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)N(NC(=O)c1c(OC)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 51.1 %

Procedure:
To a solution of 3-methyloxy-N′,2-diphenyl-4-quinolinecarbohydrazide (100 mg, 0.27 mmol) and Et3N (56 μL, 0.41 mmol) in CH2Cl2 (7 mL) was added methyl chloroformate (27 μL, 0.35 mmol). After stirring at room temperature for 4 h the mixture was diluted with CH2Cl2 and washed with 1N HCl (20 mL), 1N NaOH (20 mL) and brine (20 mL). The organic phase was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with isohexane:ethyl acetate (2:1), to afford the title compound (59 mg, 51%) as a colourless foam. 1H NMR (CDCl3, 360 MHz), δ 8.43 (1H, s), 8.16-8.13 (2H, m), 8.02-8.00 (2H, m), 7.69 (1H, dt, J=6.9 and 1.3 Hz), 7.61-7.41 (8H, m), 7.30 (1H, t, J=7.4 Hz), 3.91 (3H, s), 3.57 (3H, s). MS (ES+) C25H21N3O4 requires: 427, found: 428 (M+H+, 100%).