Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([NH:14][C@@H:15]1[CH2:20][CH2:19][C@H:18](OS(C)(=O)=O)[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[SH:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([NH:37][C:38](=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[N:32][CH:31]=[CH:30]2>CC(N(C)C)=O>[C:7]([O:11][C:12](=[O:13])[NH:14][C@H:15]1[CH2:16][CH2:17][C@H:18]([S:26][C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[C:33]([NH:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[N:32][CH:31]=[CH:30]3)[CH2:19][CH2:20]1)([CH3:8])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](OS(C)(=O)=O)CC1
Reactant: O=C(Nc1nccc2cc(S)ccc12)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Sc2ccc3c(NC(=O)c4ccccc4)nccc3c2)CC1

Procedure:
Potassium carbonate (160 mg) and methanesulfonic acid cis-4-tert-butoxycarbonylaminocyclohexyl ester (140 mg, 0.47 mmol) were added to a solution of N-(6-mercaptoisoquinolin-1-yl)benzamide residue in DMA (4 ml). The mixture was irradiated in a microwave at 120° C. for 600 s then concentrated in vacuo to give a residue. The residue was purified by preparative HPLC to give trans-[4-(1-benzoylaminoisoquinolin-6-ylsulfanyl)cyclohexyl]carbamic acid tert-butyl ester. Glacial acetic acid (1 ml) and 6M hydrochloric acid (2 ml) were added to the trans-[4-(1-benzoylaminoisoquinolin-6-ylsulfanyl)cyclohexyl]carbamic acid tert-butyl ester and the mixture was refluxed for 24 h. The mixture was then concentrated in vacuo to give a residue. The residue was loaded onto a pre-acidified SCX column using methanol and then eluted with 2M ammonia in methanol to give cude trans-6-(4-aminocyclohexylsulfanyl)isoquinolin-1-ylamine, which was further purified using prep-HPLC (9 mg), EIMS: m/z=274.5 [M+H]+
Reaction SMILES: [NH2:1][C:2]1[C:21]([N+:22]([O-])=O)=[CH:20][CH:19]=[CH:18][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.C(OCC)(=O)C.[H][H].[ClH:33]>[Pd].CO.O1CCOCC1>[ClH:33].[ClH:33].[NH2:1][C:2]1[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2cccc([N+](=O)[O-])c2N)CC1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2cccc(N)c2N)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a Parr hydrogenation bottle was added 7.0 g of tert-butyl 4-(2-amino-3-nitrophenoxy)piperidine-1-carboxylate, 10% palladium on carbon (50% w/w water) (2.0 g, wet), ethyl acetate (100 mL) and MeOH (150 mL). The atmosphere of the vessel was replaced by hydrogen gas. The reaction was shaken on a Parr hydrogenator at 40 psi at room temperature, overnight. The catalyst was filtered through a plug of Celite and the filtrate was concentrated under reduced pressure to give a residue, which was dissolved in methanol, cooled in an ice bath and carefully acidified with 4 N hydrogen chloride in 1,4-dioxane and filtered. The resulting filtrate was concentrated under reduced pressure to give of tert-butyl 4-(2,3-diaminophenoxy)piperidine-1-carboxylate dihydrochloride (6.7 g), and was used directly in the next step without any further purification. MS (EI): 308 (MH+).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([CH3:14])([CH3:13])[CH3:12])[C:6]=1[OH:15])([CH3:4])([CH3:3])[CH3:2].[C:16]([OH:20])(=[O:19])[CH:17]=O.[ClH:21]>C(O)(=O)C>[C:11]([C:7]1[CH:8]=[C:9]([CH:17]([Cl:21])[C:16]([OH:20])=[O:19])[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=1[OH:15])([CH3:14])([CH3:13])[CH3:12]
Reactant: O=CC(=O)O
Reactant: CC(C)(C)c1cccc(C(C)(C)C)c1O
Reactant: Cl
Solvent: CC(=O)O
Product: CC(C)(C)c1cc(C(Cl)C(=O)O)cc(C(C)(C)C)c1O
Temperature: 10 °C

Procedure:
309.5 g (1.5 Mol) of 2,6-di-tert-butylphenol and 266.5 g (1.8 mol) of 50% aqueous glyoxylic acid are dissolved in 1400 ml of glacial acetic acid. Then, 200 g (5.5 mol) of gazeous hydrogen chloride are introduced into this solution over a period of 2.5 hours under stirring and cooling in an ice bath to keep the temperature in the 10°-25° C. range. The mixture is then stirred at room temperature overnight, cooled to 10° C., the solid is isolated by filtration on a Buechner funnel and washed with 1000 ml water. The slightly yellow and still wet cake of the intermediate product weighs about 565 g.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][SH:6].[CH3:7]I.[OH-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1.Cl>O.C(N(CC)CC)C>[CH3:7][S:6][CH2:5][CH2:4][NH:3][C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CI
Reactant: NCCS
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCN(CC)CC
Product: CSCCNc1ccc([N+](=O)[O-])cc1
Temperature: 28.5 °C
Reaction time: 1 h
Yield: 35.3 %

Procedure:
2-aminoethanethiol dihydrochloride (45.4 g, 0.4 mol), water (100 mL), and 56.8 g (0.4 mol) of methyl iodide were mixed together. 16.5 g of sodium hydroxide pellets (0.4 mol) were dissolved in 100 mL of water and this solution was poured dropwise into the reaction mixture, while maintaining the temperature between 27-30° C. The resulting mixture was then stirred for 1 hour at 40° C. 21.2 g (10.2 mol) of para-fluoronitrobenzene and then 42 mL of triethylamine were added and the mixture was maintained in a boiling water bath for 3 hours. The resulting mixture was left overnight at room temperature and then acidified with hydrochloric acid and extracted with ethyl acetate. After evaporation to dryness, the 30 g of oil obtained were dissolved in 100 mL of 36% HCl. The resulting solution was extracted with ethyl ether to remove the starting material and, when cold, the aqueous phase was neutralized with aqueous ammonia. The resulting aqueous phase was extracted again with ethyl ether, dried, and evaporated to dryness to give 11 g of oil.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][C:10]([OH:21])([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][N:12]2[CH:16]=[N:15][CH:14]=[N:13]2)=[C:6]([CH3:24])[CH:5]=1.I[CH3:26]>O1CCOCC1>[Cl:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][C:10]([O:21][CH3:26])([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][N:12]2[CH:16]=[N:15][CH:14]=[N:13]2)=[C:6]([CH3:24])[CH:5]=1
Reactant: Cc1cc(Cl)ccc1OCC(O)(Cn1cncn1)C(C)(C)C
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(COc1ccc(Cl)cc1C)(Cn1cncn1)C(C)(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 53.3 %

Procedure:
27 g (0.9 mol) of 80% strength sodium hydride were introduced in portions into a solution of 290 g (0.86 mol) of 2-(4-chloro-2-methyl-phenoxy-methyl)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)-2-butanol in 1,600 ml of absolute dioxane at room temperature. The mixture was subsequently stirred at room temperature for 4 hours, and 141.9 g (1 mol) of iodomethane were then added dropwise. The reaction mixture was stirred at 40° C. for 12 hours and another 10 g (0.33 mol) of 80% strength sodium hydride were then added in portions. After the mixture had been stirred at room temperature for three hours, 57 g (0.4 mol) of iodomethane were added and the reaction mixture was subsequently stirred at room temperature for 72 hours. The suspension was filtered, the filtrate was concentrated, the oily residue was taken up in methylene chloride and the methylene chloride mixture was washed twice with water, dried over sodium sulphate and concentrated. 1,5-Naphthalenedisulphonic acid was added to the residue, in acetone, the salt which precipitated was filtered off with suction, washed with acetone and suspended in methylene chloride, and saturated sodium bicarbonate solution was added. The organic phase was separated off, washed and concentrated. 155 g (54% of theory) of 2-(4-chloro-2-methyl-phenoxymethyl)-3,3-dimethyl-2-methoxy- 1-(1,2,4-triazol-1-yl)butane were obtained as a light yellow oil of refractive index nD20 =1.5390.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]([NH:20][C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1.[N+:26]([C:29]1[CH:34]=[CH:33][C:32]([N:35]2[C:39]([C:40]([F:43])([F:42])[F:41])=[C:38]([C:44](Cl)=[O:45])[CH:37]=[N:36]2)=[CH:31][CH:30]=1)([O-:28])=[O:27]>C1COCC1>[C:21]([NH:20][C:16]1[CH:15]=[C:14]([CH:11]2[CH2:12][CH2:13][N:8]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:44]([C:38]3[CH:37]=[N:36][N:35]([C:32]4[CH:33]=[CH:34][C:29]([N+:26]([O-:28])=[O:27])=[CH:30][CH:31]=4)[C:39]=3[C:40]([F:41])([F:42])[F:43])=[O:45])[CH2:9][CH2:10]2)[CH:19]=[CH:18][CH:17]=1)(=[O:25])[CH:22]([CH3:23])[CH3:24]
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCCN)CC2)c1
Reactant: O=C(Cl)c1cnn(-c2ccc([N+](=O)[O-])cc2)c1C(F)(F)F
Solvent: C1CCOC1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCCNC(=O)c3cnn(-c4ccc([N+](=O)[O-])cc4)c3C(F)(F)F)CC2)c1

Procedure:
Prepared by Procedure Q1 (THF) and Scheme AT using N-{3-[1-(6-aminohexyl)-4-piperidinyl]phenyl}-2-methylpropanamide and 1-(4-nitrophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carbonyl chloride: ESMS m/e: 629.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH:18]=[O:19])=[C:13]2[C:17]=1[NH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:27](OC(=O)C)(=[O:29])[CH3:28]>CN(C)C1C=CN=CC=1.ClCCl>[C:27]([N:16]1[C:17]2[C:13](=[C:12]([CH:18]=[O:19])[CH:11]=[CH:10][C:9]=2[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:14]=[CH:15]1)(=[O:29])[CH3:28]
Reactant: O=Cc1ccc(OCc2ccccc2)c2[nH]ccc12
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)n1ccc2c(C=O)ccc(OCc3ccccc3)c21
Temperature: 25 °C
Reaction time: 24 h

Procedure:
500 mg of 7-benzyloxy-4-formylindole is combined with 50 mg of 4-dimethylaminopyridine, 0.7 ml of triethylamine, 0.5 ml of acetic anhydride, and 10 ml of dichloromethane and agitated for 24 hours at room temperature. The reaction mixture is then diluted with 50 ml of dichloromethane, washed with concentrated sodium bicarbonate solution; the organic phase is dried and concentrated. The residue is recrystallized from isopropanol, thus obtaining 400 mg of 1-acetyl-7-benzyloxy-4-formylindole, mp 77°-78° C.
Reaction SMILES: NC1C=C(OC)C(OC)=CC=1C1CCC2C=C(O)C=CC=2C1.[CH2:23]([NH:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH3:35])=[CH:28][C:27]=1[CH:36]1[CH2:45][CH2:44][C:43]2[CH:42]=[C:41]([OH:46])[CH:40]=[CH:39][C:38]=2[CH2:37]1)[CH3:24].[N:47]1([CH2:54][CH2:55][O:56][C:57]2[CH:64]=[CH:63][C:60]([CH:61]=O)=[CH:59][CH:58]=2)[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1>>[N:47]1([CH2:54][CH2:55][O:56][C:57]2[CH:64]=[CH:63][C:60]([CH2:61][CH2:24][CH2:23][NH:25][C:26]3[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH3:35])=[CH:28][C:27]=3[CH:36]3[CH2:45][CH2:44][C:43]4[CH:42]=[C:41]([OH:46])[CH:40]=[CH:39][C:38]=4[CH2:37]3)=[CH:59][CH:58]=2)[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1
Reactant: O=Cc1ccc(OCCN2CCCCCC2)cc1
Reactant: CCNc1cc(OC)c(OC)cc1C1CCc2cc(O)ccc2C1
Agent: COc1cc(N)c(C2CCc3cc(O)ccc3C2)cc1OC
Product: COc1cc(NCCCc2ccc(OCCN3CCCCCC3)cc2)c(C2CCc3cc(O)ccc3C2)cc1OC
Yield: 67.1 %

Procedure:
Synthesized from 6-(2-amino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol according to an analogous synthetic method to Example 36, 6-(2-ethylamino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol (55 mg) and 4-(2-azepan-1-ylethoxy)benzaldehyde (192 mg) were used according to an analogous synthetic method to Example 38 to provide the title compound (63 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[CH2:14][CH:13]2[CH:10]([CH2:11][NH:12]2)[CH2:9]1)=[O:7].Br[C:21]1[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=1>>[CH2:28]([O:27][C:25](=[O:26])[C:24]1[CH:30]=[CH:31][C:21]([N:12]2[CH2:11][CH:10]3[CH:13]2[CH2:14][N:8]([C:6](=[O:7])[NH:5][CH2:4][C:3]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:2]=2[Cl:1])[CH2:9]3)=[CH:22][CH:23]=1)[CH3:29]
Reactant: CCOC(=O)c1ccc(Br)cc1
Reactant: O=C(NCc1ccc(Cl)cc1Cl)N1CC2CNC2C1
Product: CCOC(=O)c1ccc(N2CC3CN(C(=O)NCc4ccc(Cl)cc4Cl)CC32)cc1

Procedure:
In analogy to the experimental procedure of example 20) rac-3-(2,4-Dichloro-benzylcarbamoyl)-3,6-diaza-bicyclo[3.2.0]heptane using ethyl 4-bromobenzoate instead of 2-bromopyrimidine was converted into the title compound which was obtained as a white solid and directly used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:15]=2[Cl:22])[N:11]([CH3:23])[N:10]=1.[H-].[Na+].Cl[C:27]1[C:32]([Cl:33])=[CH:31][C:30]([C:34]([F:37])([F:36])[F:35])=[CH:29][N:28]=1.O>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][O:21][C:27]3[C:32]([Cl:33])=[CH:31][C:30]([C:34]([F:37])([F:35])[F:36])=[CH:29][N:28]=3)=[CH:16][C:15]=2[Cl:22])[N:11]([CH3:23])[N:10]=1
Reactant: FC(F)(F)c1cnc(Cl)c(Cl)c1
Reactant: Cn1nc(-c2c(F)cccc2Cl)nc1-c1ccc(CO)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cn1nc(-c2c(F)cccc2Cl)nc1-c1ccc(COc2ncc(C(F)(F)F)cc2Cl)cc1Cl
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 82.1 %

Procedure:
3-(2-chloro-6-fluorophenyl)-5-(2-chloro-4-hydroxymethylphenyl) 1-methyl-1H-1,2,4-triazole (0.50 g) is dissolved in 1,2-dimethoxyethane (20 ml) and cooled to 0° C., to which is added sodium hydride (60%, 0.07 g) and the reaction mixture is stirred for 15 minutes. Then, a solution of 2,3-dichloro-5-trifluoromethyl pyridine (0.34 g) in 1,2-dimethoxyethane (10 ml) is added dropwise and stirred for 3 hours. On completion of the reaction, the reaction solution is warmed to room temperature and poured into water and extracted with ether. The organic layer is washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography to give 0.62 g of desired compound.
Reaction SMILES: [CH:1]([NH:4][C:5]([N:7]1[CH2:12][C:11](=[O:13])[N:10]2[CH:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][CH2:16][CH:9]2[CH2:8]1)=[O:6])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[C:38](OCC)(=[O:44])[C:39](OCC)=[O:40]>CN(C=O)C>[OH:44][C:38]1[C:39](=[O:40])[N:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:6])[N:7]2[CH2:8][C@@H:9]3[CH2:16][CH2:15][C@H:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:10]3[C:11](=[O:13])[C:12]=12
Reactant: CCOC(=O)C(=O)OCC
Reactant: CC(C)NC(=O)N1CC(=O)N2C(CCC2c2ccccc2)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)n1c(=O)c(O)c2n(c1=O)C[C@@H]1CC[C@H](c3ccccc3)N1C2=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of racemic (6R,8aS)-N-isopropyl-4-oxo-6-phenylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (0.187 g, 0.620 mmol) in DMF (3 mL) at 0° C. was added a 1M solution of lithium bis(trimethylsilyl)amide in THF (1.49 mL, 1.49 mmol), followed by diethyl oxalate (0.101 mL, 0.745 mmol). The mixture was stirred for 18 h, allowing the cooling bath to warm to ambient temperature. The resultant mixture was then treated with additional lithium bis(trimethylsilyl)amide in THF (1.49 mL, 1.49 mmol) and stirred at room temperature for 6 h. The product mixture was concentrated under vacuum and the residue was partitioned between aqueous HCl and ethyl acetate. The organic extract was concentrated under vacuum. The residue was subjected to HPLC purification on C18 stationary phase eluted with water/acetonitrile/TFA mobile phase to give the title compound as a solid. HPLC RT=3.19 min, 95% at 215 nm (Method A); ES MS (M+H)=356.2; 1H NMR (400 MHz, DMSO-d6) δ 7.32-7.24 (m, 2H) 7.22-7.16 (m, 3H) 5.12-5.02 (m, 2H) 4.80-4.74 (d, 1H) 3.84-3.74 (m, 1H) 2.38-2.28 (m, 1H) 2.06-1.98 (m, 1H) 1.74-1.66 (m, 1H) 1.42-1.34 (dd, 6H) 1.34-1.26 (m, 1H).
Reaction SMILES: CS(O)(=O)=O.[CH3:6][N:7]([CH2:9][C:10]1[O:14][C:13](CO)=[CH:12][CH:11]=1)[CH3:8].[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22].[C:23](=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][O:22][CH2:23][C:11]1[CH:12]=[CH:13][O:14][C:10]=1[CH2:9][N:7]([CH3:6])[CH3:8]
Reactant: CN(C)Cc1ccc(CO)o1
Reactant: NCCCCO
Reactant: O=C([O-])[O-]
Agent: CS(=O)(=O)O
Agent: [Na+]
Solvent: C1CCOC1
Product: CN(C)Cc1occc1COCCCCN
Reaction time: 1 h

Procedure:
A solution of methanesulphonic acid (86 g), 5-[(dimethylamino)methyl]-2-furanmethanol (15.52 g), and 4-aminobutanol (17.82 g) in tetrahydrofuran (100 ml) was heated at 98°-100° for 1.5 h. After 1 h. at room temperature, excess anhydrous sodium carbonate was added and the suspension filtered after 18 h. The filtrate was evaporated, water (230 ml) added and the suspension extracted with ether (3×80 ml). The ethereal extracts were washed with water (2×50 ml), the aqueous fraction acidified with oxalic acid (25 g) and evaporated to low bulk. Excess anhydrous sodium carbonate and ethyl acetate (200 ml) were added, the suspension heated at boiling for 30 min. and the suspension filtered after 2 h. Evaporation of the filtrate yielded an oil which was distilled (100°-110°/0.08 mm) to give the title compound (6.64 g).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]=1[N:14]=[N:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:18][C:17]=1[NH:27][C:28](=[O:30])[CH3:29].C([O-])(=O)C.[K+].[CH:36]([NH2:38])=O.C(OC(=O)C)(=O)C>[Cu]I.C(OCCCC)(=O)C>[C:36]([C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]=1[N:14]=[N:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:18][C:17]=1[NH:27][C:28](=[O:30])[CH3:29])#[N:38]
Reactant: CCN(CC)c1ccc(N=Nc2c(Br)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Reactant: NC=O
Agent: [Cu]I
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CCCCOC(C)=O
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(N=Nc2c(C#N)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Temperature: 110 °C
Reaction time: 0.25 h
Yield: 95 %

Procedure:
2-Bromo-4,6-dinitro-2'-acetylamino-4'-(N,N-diethylamino) azobenzene (2.4 parts), copper (I) iodide (0.95 parts), anhydrous potassium acetate (1.5 parts), formamide (1.8 parts), acetic anhydride (2.0 parts) and n-butyl acetate (44 parts) are mixed together and heated, with stirring, to 110° C. during 15 minutes. The temperature is maintained at 110° C. for 2 hours when reaction is complete. The mixture is cooled to room temperature and poured into petroleum ether (boiling range 60-80° C.) (400 parts). The precipitate is collected, washed with petroleum ether (100 parts) and dried. 2-Cyano-4,6-dinitro-2'-acetylamino-4'-(N,N-diethylamino)azobenzene is obtained in 95% yield.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[Cl:7].[OH-].[K+].[Br:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16].Br[CH2:19][CH2:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=1.Br>C(#N)C>[Br-:10].[C:15]([CH2:14][CH2:13][CH2:12][CH2:11][N:3]1[C:2]([Cl:1])=[C:6]([Cl:7])[N+:5]([CH2:19][CH2:20][C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)=[CH:4]1)([OH:17])=[O:16]
Reactant: O=C(O)CCCCBr
Reactant: BrCCc1ccc2ccccc2c1
Reactant: Clc1nc[nH]c1Cl
Agent: Br
Agent: [K+]
Agent: [OH-]
Solvent: CC#N
Product: O=C(O)CCCCn1c[n+](CCc2ccc3ccccc3c2)c(Cl)c1Cl
Product: [Br-]

Procedure:
4,5-dichloroimidazole (1.00 g, 7.36 mmol) was dissolved in acetonitrile. Potassium hydroxide (0.828 g, 14.72 mmol) was added to the solution and allowed to reflux for 30 min. 1 equivalent of 5-bromopentanoic acid (1.33 g, 7.36 mmol) was added to the solution and refluxed for 5 h. Solution was filtered to remove the KBr precipitate and placed back onto reflux. An equivalent of 2-(2-bromoethyl)naphthalene (1.73 g, 7.36 mmol) was added to solution and refluxed for 2.5 h. The solution was neutralized with 6M HBr, volatiles removed in vacuo, and the resulting product will be collected and analyzed.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.Cl.[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([OH:30])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:60]1[CH:65]=[CH:64][C:63]([CH2:66][CH2:67]O)=[CH:62][CH:61]=1>C(Cl)Cl>[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:67][CH2:66][C:63]3[CH:64]=[CH:65][N:60]=[CH:61][CH:62]=3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1
Reactant: COC(=O)Oc1cc(Nc2ncnc3cc(O)c(OC)cc23)c(F)cc1C
Reactant: OCCc1ccncc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)Oc1cc(Nc2ncnc3cc(OCCc4ccncc4)c(OC)cc23)c(F)cc1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89.6 %

Procedure:
Diethyl azodicarboxylate (244 mg, 1.4 mmol) was added to a suspension of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (261 mg, 0.7 mmol), (prepared as described for the starting material in Example 22), triphenylphosphine (367 mg, 1.4 mmol) and 2-(4-pyridyl)ethanol (104 mg, 0.84 mmol), (Zhur. Obshchei. Khim. 1958, 28, 103-110), in methylene chloride and the mixture stirred for 30 minutes at ambient temperature. The solvent was removed by evaporation. The residue was suspended in ether and the ether then decanted. The resulting crude oil was purified by column chromatography eluting with methylene chloride/methanol (90/10) to give 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline (300 mg, 90%).
Reaction SMILES: O=[CH:2][C@H:3]([C@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].[OH2:11].[CH2:12]([NH2:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]>C(O)(C)C>[CH:9]1([N:24]([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH3:12])[C:12](=[O:11])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[O:10][CH2:2][C@@H:3]([OH:4])[C@H:5]([OH:6])[C@@H:7]1[OH:8]
Reactant: O=C[C@@H](O)[C@@H](O)[C@H](O)CO
Reactant: CCCCCCCCCCCCN
Reactant: O
Solvent: CC(C)O
Product: CCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)C1OC[C@@H](O)[C@H](O)[C@@H]1O
Temperature: 25 °C

Procedure:
10 g of D-lyxose are dissolved in 120 ml of isopropanol and 60 ml of water and the solution is warmed to 70° C. 18 g of dodecylamine are added. After a clear solution has formed, the temperature is maintained for a further 15 minutes. The mixture is cooled to room temperature and evaporated in vacuo. 10 g of the resulting syrup are dissolved in 100 ml of tetrahydrofuran and 10 ml of methanol, and 10 g of sodium carbonate are added. 5.5 g of dodecanoic acid chloride, dissolved in 20 ml of tetrahydrofuran, are added dropwise at 0° C. When the reaction has ended, the mixture is worked up, and the product purified, as described in Example 2.
Reaction SMILES: [C:1](OCC)(OCC)(OCC)[CH2:2]C.[CH3:13][NH:14][C:15](=[O:24])[C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[NH2:23].[C:25](=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:22][C:19]1[CH:18]=[C:17]2[C:16]([C:15](=[O:24])[N:14]([CH3:25])[C:13]([CH2:1][CH3:2])=[N:23]2)=[CH:21][CH:20]=1
Reactant: CNC(=O)c1ccc(Br)cc1N
Reactant: CCOC(CC)(OCC)OCC
Reactant: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: CCc1nc2cc(Br)ccc2c(=O)n1C
Temperature: 100 °C
Reaction time: 1 h

Procedure:
1.5 ml of triethyl orthopropionate and 30 μL of acetic acid were added to 1 ml solution of N-methyl-2-pyrolidine with 796 mg of N-methyl-2-amino4-bromobenzamide, and the mixture was stirred at 100° C. for 1 hour. Saturated sodium bicarbonate aqueous solution was added to the reaction solution, and extracted with ether. Ether layer was washed with saturated saline solution, and dried with anhydrous magnesium sulfate. After distilling out the solvents under reduced pressure, the residues were separated and purified by silicagel column chromatography (hexane/ethyl acetate=4/1), to obtain 653 mg of the above compound as a colorless solid.