Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)[C:6]([C:19]([OH:21])=O)=[CH:5]2.[NH2:22][C:23]1[CH:24]=[C:25]2[N:31]=[CH:30][S:29][C:26]2=[N:27][CH:28]=1>>[N:31]1[C:25]2[C:26](=[N:27][CH:28]=[C:23]([NH:22][C:19]([C:6]3[N:7]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)[C:8]4[C:4]([CH:5]=3)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)=[O:21])[CH:24]=2)[S:29][CH:30]=1
Reactant: O=C(O)c1cc2cc(F)ccc2n1Cc1cccc(F)c1
Reactant: Nc1cnc2scnc2c1
Product: O=C(Nc1cnc2scnc2c1)c1cc2cc(F)ccc2n1Cc1cccc(F)c1
Yield: 72.9 %

Procedure:
The process is performed according to a method similar to that of Example 1.2, starting with 0.32 g (1.11 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid prepared in step 1.1 and 0.2021 g (1.34 mmol) of 6-amino-thiazolo[5,4-b]pyridine (WO2007/100758). At the end of the reaction, the product is concentrated under reduced pressure and then taken up in 100 mL of water. A precipitate is collected by filtration, and is purified by chromatography on a column of alumina, eluting with a mixture of dichloromethane and methanol. The resulting product is recrystallized from methanol, and a solid is collected by filtration and dried under reduced pressure. 340 mg of the expected product are thus isolated.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]2[CH2:6][CH2:7][CH2:8][C:9](=[O:12])[C:10]=2[CH:11]=1.[C:13]([NH:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1)(=[O:15])[CH3:14].N1CCCCC1>C(OCC)(=O)C>[C:13]([NH:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[C:8]2[CH2:7][CH2:6][C:5]3[N:4]=[CH:3][C:2]([CH3:1])=[CH:11][C:10]=3[C:9]2=[O:12])=[CH:19][CH:18]=1)(=[O:15])[CH3:14]
Reactant: Cc1cnc2c(c1)C(=O)CCC2
Reactant: CC(=O)Nc1ccc(C=O)cc1
Solvent: CCOC(C)=O
Solvent: C1CCNCC1
Product: CC(=O)Nc1ccc(C=C2CCc3ncc(C)cc3C2=O)cc1
Temperature: 110 °C
Yield: 73.7 %

Procedure:
7,8-Dihydro-3-methylquinoline-5[6H]one (8 g) was mixed with 4-acetamidobenzaldehyde (9 g) and piperidine (0.5 ml) and heated at 110° C. for 3 hours. Ethyl acetate (30 ml) was added to the hot reaction mixture and the mixture allowed to cool. Crystals formed and were isolated by filtration, then washed with diethyl ether to give the title compound (11.2 g). A portion was recrystallised from ethyl acetate to give an analytical sample, mp 226°-228° C.
Reaction SMILES: N1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]=2[N:4]=[C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])N=1.C(O)(=O)[C:17]1[C:18](=[CH:20][CH:21]=[CH:22][CH:23]=1)N.C(ON=O)CC(C)C>O1CCOCC1.C(OCC)C>[CH2:7]1[C:6]2[C:5](=[N:4][C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:17]3[C:18]=2[CH:20]=[CH:21][CH:22]=[CH:23]3)[CH2:10][CH2:9][CH2:8]1
Reactant: Nc1ccccc1C(=O)O
Reactant: CCOC(=O)c1nnc2c(n1)CCCC2
Agent: CC(C)CCON=O
Solvent: CCOCC
Solvent: C1COCCO1
Product: CCOC(=O)c1nc2c(c3ccccc13)CCCC2

Procedure:
Analogously to the method described by Gonsalves et al. (Tetrahedron 1992, 48, 6821) a solution of 3.90 g of ethyl 5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-carboxylate (Sagi et al., Heterocycles 1989, 29, 2253) in 20 ml dioxane is refluxed. Then 8.22 g of anthranilic acid and 7.02 g of isoamylnitrite, in each case dissolved in 20 ml dioxane, are simultaneously added dropwise within 25 minutes by means of two dropping funnels. The reaction mixture is refluxed for a further 30 minutes. For working up the cooled deep-brown reaction solution is diluted with 150 ml diethyl ether, washed with 100 ml of 2 N sodium hydroxide solution and with water, dried over magnesium sulphate and evaporated down. The brown, oily flask residue is chromatographed through a silica gel column with ethyl acetate/petroleum ether (20:80 to 50:50) as eluant. The product obtained is still somewhat contaminated, but is reacted further without any more purification.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4](/[CH:7]=[CH:8]/[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:3][CH:2]=1.[H][H]>CO.[Pd]>[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:3][CH:2]=1
Reactant: CCOC(=O)/C=C/c1ccncc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)CCc1ccncc1

Procedure:
Ethyl (E)-3-pyridin-4-ylprop-2-enoate (Method 8; 102.3 g, 576 mmol) in MeOH (300 ml) was hydrogenated using palladium on carbon 5% (9.0 g) under atmospheric pressure hydrogen for 72 hours. The catalyst was filtered off through diatomaceous earth and the filtrate concentrated to give a yellow oil. Yield 103.1 g (99%). NMR (300 MHz, CDCl3) 8.50 (d, 2H), 7.15 (d, 2H), 4.12 (q, 2H), 2.95 (t, 2.64 (t, 2H), 1.21 (t, 3H); m/z 180.4.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:12][C:9]1[CH:10]=[CH:11][C:2]([C:13]#[N:14])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: CN(C)C=O
Reactant: COC(=O)c1cc(Cl)ccc1Br
Agent: [C-]#N
Agent: [Zn+2]
Product: COC(=O)c1cc(Cl)ccc1C#N
Temperature: 90 °C

Procedure:
To a solution of methyl 2-bromo-5-chlorobenzoate (1.15 g, 4.6 mmol) in degassed DMF was added zinc cyanide (282 mg, 2.40 mmol) and palladium tetrakis triphenylphosphine (100 mg, 0.086 mmol) and the reaction is stirred at 90° C. over night. The reaction was partitioned between ethyl acetate and water. The organic was concentrated in vacuo and purified by flash chromatography eluting a gradient to 10 to 25% ethyl acetate in hexane yielding a white solid (methyl 5-chloro-2-cyanobenzoate).
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:19])[NH:5][C:6](=[O:18])[NH:7][C:8]=1[O:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[CH:11]=1)[CH3:2].[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25]Br)#[N:21]>>[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][N:7]1[C:8]([O:9][C:10]2[CH:11]=[C:12]([CH3:17])[CH:13]=[C:14]([CH3:16])[CH:15]=2)=[C:3]([CH2:1][CH3:2])[C:4](=[O:19])[NH:5][C:6]1=[O:18])#[N:21]
Reactant: CCc1c(Oc2cc(C)cc(C)c2)[nH]c(=O)[nH]c1=O
Reactant: N#Cc1cccc(CBr)c1
Product: CCc1c(Oc2cc(C)cc(C)c2)n(Cc2cccc(C#N)c2)c(=O)[nH]c1=O
Yield: 57.5 %

Procedure:
5-Ethyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedione and 3-cyanobenzyl bromide were reacted by the same way with the example 1 to obtain the titled compound (216 mg, yield: 57.5%).
Reaction SMILES: C(OC([NH:8][C@H:9]([CH2:13][CH2:14][NH:15][C:16]([C:18]1[N:19]=[C:20]([C:36]#[N:37])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:22]=2)=[O:17])[C:10]([OH:12])=[O:11])=O)(C)(C)C.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]>C(Cl)Cl>[NH2:8][C@H:9]([CH2:13][CH2:14][NH:15][C:16]([C:18]1[N:19]=[C:20]([C:36]#[N:37])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:22]=2)=[O:17])[C:10]([OH:12])=[O:11].[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]
Reactant: CC(C)(C)OC(=O)N[C@H](CCNC(=O)c1nc(C#N)c2cc(Oc3ccccc3)ccc2c1O)C(=O)O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1nc(C(=O)NCC[C@@H](N)C(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
(R)-2-(tert-Butoxycarbonylamino)-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)butanoic acid (40 mg, 0.06 mmol) was dissolved in TFA (4 mL) and CH2Cl2 (4 mL). The resulting mixture was stirred at room temperature for 3 hours. The volatiles were removed in vacuo and the residue was dissolved again in CH2Cl2 (4 mL). The volatiles were removed again in vacuo to give the title compound as its TFA salt in 19 mg. MS: (−) m/z 405.27 (M−1).
Reaction SMILES: Cl.Cl.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19])[CH2:8][N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:41]=[C:42]([O:46][CH3:47])[C:43]=1[O:44][CH3:45])[C:38]([Cl:40])=[O:39]>O>[ClH:40].[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:41]=[C:42]([O:46][CH3:47])[C:43]=1[O:44][CH3:45])[C:38]([N:12]1[CH2:11][CH2:10][N:9]([CH2:8][C:7]2[CH:15]=[C:16]([O:20][CH3:21])[C:17]([O:18][CH3:19])=[C:5]([O:4][CH3:3])[CH:6]=2)[CH2:14][CH2:13]1)=[O:39]
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Reactant: COc1cc(CN2CCNCC2)cc(OC)c1OC
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: COc1cc(CN2CCN(C(=O)c3cc(OC)c(OC)c(OC)c3)CC2)cc(OC)c1OC
Temperature: 25 °C
Yield: 68.3 %

Procedure:
To a mixture of 1-(3,4,5-trimethoxybenzyl)piperazine dihydrochloride (0.6 g), sodium bicarbonate (5 g), ethyl acetate (20 ml) and water (20 ml) is added, with stirring at room temperature, 3,4,5-trimethoxybenzoyl chloride (0.61 g), followed by stirring for 30 minutes. The ethyl acetate layer is separated, washed with water, dried, and concentrated under reduced pressure. The residue is dissolved in ethanol (10 ml). To the solution is added a solution of hydrogen chloride - ethanol (1 ml). The mixture is diluted with ethyl ether (100 ml) to give 1-(3,4,5-trimethoxybenzoyl)-4-(3,4,5-trimethoxybenzyl)piperazine hydrochloride (0.6 g) as colorless needles, m.p. 200°-205° C. (decomp.).
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C@H:7]1[CH2:10][C@@H:9]([NH2:11])[CH2:8]1)=[O:6])[CH3:3].[CH2:12]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:26]=[C:25]([C:27]3[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=3)[O:24][N:23]=2)=[CH:18][CH:17]=1)[CH:13]([CH3:15])[CH3:14].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:12]([C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:26]=[C:25]([C:27]3[CH:28]=[CH:29][C:30]([CH2:31][NH:11][C@@H:9]4[CH2:10][C@H:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])[CH2:8]4)=[CH:33][CH:34]=3)[O:24][N:23]=2)=[CH:20][CH:21]=1)[CH:13]([CH3:15])[CH3:14]
Reactant: CCOC(=O)[C@H]1C[C@@H](N)C1
Reactant: CC(C)Cc1ccc(-c2noc(-c3ccc(C=O)cc3)n2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCOC(=O)[C@H]1C[C@@H](NCc2ccc(-c3nc(-c4ccc(CC(C)C)cc4)no3)cc2)C1
Reaction time: 0.5 h
Yield: 55.5 %

Procedure:
cis-3-Amino-cyclobutanecarboxylic acid ethyl ester hydrochloride (0.193 g, 1.35 mmol) was added to a solution of 4-[3-(4-isobutylphenyl)-1,2,4-oxadiazol-5-yl]benzaldehyde (0.333 g, 1.08 mmol), acetic acid (2 mL) and THF (18 mL) and stirred for 30 minutes. Sodium triacetoxyborohydride (0.500 g, 2.36 mmol) was added to the reaction mixture, stirred at room temperature for 16 hours, and concentrated in vacuo to give a white solid. The solid was triturated with water, filtered and dried to give the title compound (0.260 g, 55% yield) as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[NH:16][C:15](/[CH:17]=[CH:18]/[C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]4)=[C:21]([O:31][CH3:32])[CH:20]=3)=[N:14][N:13]=2)[CH2:9][CH2:10]O)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:35])=O>>[Cl:35][CH2:10][CH2:9][CH:8]([C:12]1[NH:16][C:15](/[CH:17]=[CH:18]/[C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]3)=[C:21]([O:31][CH3:32])[CH:20]=2)=[N:14][N:13]=1)[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1cc(/C=C/c2nnc(C(CCO)c3ccc(F)cc3)[nH]2)ccc1-n1cnc(C)c1
Product: COc1cc(/C=C/c2nnc(C(CCCl)c3ccc(F)cc3)[nH]2)ccc1-n1cnc(C)c1
Temperature: 25 °C

Procedure:
A solution of 3-(4-fluorophenyl)-3-{5-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-4H-[1,2,4]triazol-3-yl}propan-1-ol (83 mg) in phosphorus oxychloride (1 mL) was stirred at 120° C. for one hour. The reaction solution was left to cool to room temperature and then concentrated under reduced pressure. Ethyl acetate and saturated sodium bicarbonate water were added to the residue, and the organic layer was separated. The resulting organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 86 mg of the title compound. The property value of the compound is as follows.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6](=[O:12])[C:7]([O:9]CC)=[O:8])=[CH:2]1.[OH-].[Na+].CO>O>[S:1]1[CH:5]=[CH:4][C:3]([C:6](=[O:12])[C:7]([OH:9])=[O:8])=[CH:2]1
Reactant: CCOC(=O)C(=O)c1ccsc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C(=O)c1ccsc1
Reaction time: 1 h

Procedure:
To a mixture of ethyl thien-3-yl-glyoxylate (10 g) and 2 N-sodium hydroxide (50 ml) was added sufficient methanol to produce a homogeneous solution, and the reaction was allowed to stand at room temperature for one hour. The solution was poured into water, extracted with ether, acidified with 2 N-hydrochloric acid and extracted with ether. The combined extracts were dried and evaporated to give an oil which was triturated with benzene-petroleum ether, and the resulting solid filtered and dried (7.5 g; 88%), m.p. 63°, νmax. (Nujol) 3600 and 1702 cm-1 (CO2H), τ (DMSO-d6) values include 1.29, 2.21, 2.38 (thien-3-yl protons).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[S:7][C:6]([N:8]2[CH:13]([OH:14])[CH2:12][CH2:11][N:10]([CH3:15])[C:9]2=[O:16])=[N:5][N:4]=1.[CH3:19][N:20]([CH3:24])[C:21](Cl)=[O:22].N1C=CC=CC=1>C1(C)C=CC=CC=1>[F:18][C:2]([F:1])([F:17])[C:3]1[S:7][C:6]([N:8]2[CH:13]([O:14][C:21](=[O:22])[N:20]([CH3:24])[CH3:19])[CH2:12][CH2:11][N:10]([CH3:15])[C:9]2=[O:16])=[N:5][N:4]=1
Reactant: CN1CCC(O)N(c2nnc(C(F)(F)F)s2)C1=O
Reactant: CN(C)C(=O)Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CN(C)C(=O)OC1CCN(C)C(=O)N1c1nnc(C(F)(F)F)s1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole), N,N-dimethylcarbamoyl chloride (0.06 mole), pyridine (0.06 mole) and toluene (150 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 3 hours. After this time the reaction mixture is cooled to room temperature and is filtered to remove pyridine hydrochloride. The filtrate is then washed with water, dried over anhydrous magnesium sulfate and stripped of solvent leaving a residue. The residue is recrystallized to yield the desired product tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N,N-dimethylcarbamoyloxy-2(1H)-pyrimidinone.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[N:6][C:5]([O:8]C)=[C:4]2[N:10]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH:11]=[CH:12][C:3]=12.Cl>O1CCOCC1>[Br:1][C:2]1[C:3]2[CH:12]=[CH:11][N:10]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[C:4]=2[C:5](=[O:8])[NH:6][CH:7]=1
Reactant: COc1ncc(Br)c2ccn(S(=O)(=O)c3ccc(C)cc3)c12
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ccc(S(=O)(=O)n2ccc3c(Br)c[nH]c(=O)c32)cc1
Temperature: 40 °C
Reaction time: 16 h
Yield: 93.9 %

Procedure:
A solution of Example 1c (12.4 g, 32.6 mmol) in dioxane (140 mL) was stirred at room temperature. To this solution was added 4M HCl in dioxane (140 mL). The reaction mixture was stirred at 40° C. for 16 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was triturated with diethylether, filtered, and rinsed with additional diethylether and dried to provide the title compound (11.23 g, 30.6 mmol, 94% yield) as a beige solid.
Reaction SMILES: [CH2:1]([N:4]([CH2:10][CH:11]=O)[C:5](=[O:9])[O:6][CH2:7][CH3:8])[CH:2]=[CH2:3].[CH3:13][NH:14][C@H:15](C(O)=O)[CH3:16]>C1(C)C=CC=CC=1>[CH3:13][N:14]1[CH:15]([CH3:16])[CH2:3][CH:2]2[CH:11]1[CH2:10][N:4]([C:5]([O:6][CH2:7][CH3:8])=[O:9])[CH2:1]2
Reactant: CN[C@@H](C)C(=O)O
Reactant: C=CCN(CC=O)C(=O)OCC
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CC2CC(C)N(C)C2C1

Procedure:
17.2 g (0.1 mol) of ethyl N-allyl-N-(2-oxoethyl)-carbamate are heated under reflux overnight with 10.5 g (0.1 mol) of N-methylalanine in 300 ml of toluene. The mixture is concentrated and the residue is distilled.
Reaction SMILES: C1(S([CH2:10][C:11]2[N:15]=[C:14]([C:16]3[O:17][CH:18]=[CH:19][CH:20]=3)[NH:13][N:12]=2)(=O)=O)C=CC=CC=1.[F:21][C:22]([F:38])([F:37])[C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][C:35]#[N:36])[CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1>>[F:21][C:22]([F:37])([F:38])[C:23]1[CH:24]=[C:25]([C:33]2[CH:34]=[C:35]([NH2:36])[N:12]3[N:13]=[C:14]([C:16]4[O:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[C:11]3[CH:10]=2)[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1
Reactant: N#CC=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: O=S(=O)(Cc1n[nH]c(-c2ccco2)n1)c1ccccc1
Product: Nc1cc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc2nc(-c3ccco3)nn12

Procedure:
The title compound, MS m/e (%): 412 (M+, 100), was prepared in accordance with the general method of example 1 from 3-benzenesulfonylmethyl-5-furan-2-yl-1H-[1,2,4]triazole and 3-[3,5-bis(trifluoromethyl)phenyl]acrylonitrile.
Reaction SMILES: [OH:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6].N1C=CC=CC=1.[Br:16][CH2:17][CH2:18][CH2:19][S:20](Cl)(=[O:22])=[O:21]>C(OCC)C>[Br:16][CH2:17][CH2:18][CH2:19][S:20]([O:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6])(=[O:22])=[O:21]
Reactant: COP(=O)(CCO)OC
Reactant: O=S(=O)(Cl)CCCBr
Solvent: c1ccncc1
Solvent: CCOCC
Product: COP(=O)(CCOS(=O)(=O)CCCBr)OC
Reaction time: 24 h

Procedure:
3.9 g of dimethyl 2-hydroxyethylphosphonate and 5.9 g of pyridine were dissolved in 40 ml. of dry diethyl ether, and the solution was cooled with ice to -5° C. A solution of 6.0 g of γ-bromopropylsulfonyl chloride in 30 ml. of dry diethyl ether was added dropwise to the cooled solution by means of a dropping funnel. After the addition, the mixed solution was allowed to stand for 24 hours at 0° to 5° C. The reaction mixture was poured into 50 ml. of 5% hydrochloric acid, and extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off at reduced pressure. The product was further dried at room temperature at 0.7 mmHg for 18 hours to afford dimethyl 2-(3-bromopropylsulfonyloxy)ethylphosphonate as a colorless oil in a yield of 75 mol %. The product showed the following characteristic values.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C@H:5]([N:27]1[C:35]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:34]2[C:29]([N:30]([CH3:45])[C:31](=[O:44])[N:32]([CH3:43])[C:33]2=[O:42])=[CH:28]1)[CH2:6][S:7]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH3:3].C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[CH3:1][N:2]([CH3:3])[CH2:4][C@H:5]([N:27]1[C:35]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:34]2[C:29]([N:30]([CH3:45])[C:31](=[O:44])[N:32]([CH3:43])[C:33]2=[O:42])=[CH:28]1)[CH2:6][SH:7]
Reactant: CN(C)C[C@@H](CSC(c1ccccc1)(c1ccccc1)c1ccccc1)n1cc2c(c1-c1ccccc1)c(=O)n(C)c(=O)n2C
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN(C)C[C@@H](CS)n1cc2c(c1-c1ccccc1)c(=O)n(C)c(=O)n2C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
6-((S)-1-Dimethylaminomethyl-2-tritylsulfanyl-ethyl)-1,3-dimethyl-5-phenyl-1,6-dihydro-pyrrolo[3,4-d]pyrimidine-2,4-dione (step 4) (1.3 g, 2.115 mmol) was dissolved in DCM (50 mL) and TFA (5 mL, 64.9 mmol) and triethylsilane (0.675 mL, 4.23 mmol) were added. The mixture was stirred at RT for 1 hour 20 mins. The reaction mixture was rigorously evaporated under vacuum. Purification by chromatography on silica, eluting with 20-100% EtOAc/hexane, 10% MeOH/EtOAc and 10% (7N NH3 in MeOH)/EtOAc gave the title compound.
Reaction SMILES: [CH3:1][C:2]1([OH:8])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.N1C=CC=CC=1.Cl[C:16]([O:18][CH2:19][Cl:20])=[O:17]>ClCCl>[C:16](=[O:17])([O:8][C:2]1([CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1)[O:18][CH2:19][Cl:20]
Reactant: CC1(O)CCCCC1
Reactant: O=C(Cl)OCCl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1(OC(=O)OCCl)CCCCC1
Reaction time: 2 h

Procedure:
1-Methylcyclohexanol (4.57 g) in dichloromethane (40 ml) was cooled in an ice-bath and treated with pyridine (3.24 ml). Chloromethyl chloroformate (3.65 ml) in dichloromethane (10 ml) was added dropwise through a pressure-equalising funnel. The mixture was stirred for 2 h and then washed with water (2×), dried (MgSO4) and then evaporated to leave a reddish-coloured oil, which was dissolved in dichloromethane and filtered through silica gel (230-400 mesh ASTM) to give (after evaporation) chloromethyl 1-methylcyclohexyl carbonate as a colourless oil (8.97 g), υmax(CH2Cl2) 2940, 2865, 1763, 1444, 1346, 1292, and 1237 cm−1; δ(CDCl3) 1.25-1.70 (11H, m), 2.12-2.18 (2H, m), 5.69 (2H,s) ppm.
Reaction SMILES: [C:1]([CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]1)#[N:2].N.[H][H]>CO.[Ni]>[NH2:2][CH2:1][CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]1
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CC#N)OC(C)(C)O1
Agent: [Ni]
Agent: N
Solvent: CO
Product: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CCN)OC(C)(C)O1
Reaction time: 16 h

Procedure:
A solution of (4R-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, (Example 1) 5.63 g (0.048 mol), in 100 mL of methanol saturated with gaseous ammonia is treated with 0.5 g of Raney nickel #30 and hydrogen gas in a shaker at 50 pounds per square inch (psi) and 40° C. After 16 hours, thin layer chromatography indicates no starting nitrile present. The suspension is cooled, filtered through filter aid, and concentrated to an oil. This crude oil is purified by flash chromatography on silica gel with 30:20:1 (ethyl acetate:methanol:ammonium hydroxide) as eluant to give 4.93 g of (4R-cis)-1,1-dimethylethyl 6-(2-aminoethyl) -2,2-dimethyl-1,3-dioxane-4-acetate (98.2 area %) as a clear oil.
Reaction SMILES: N[C:2]1[C:15]2C(=S)[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([C:18]2C=CC=CC=2)=[CH:4][C:3]=1Br.[OH:25]CCS(C1C=C(O)C=CC=1)(=O)=O>>[CH:12]1[C:13]2[C:18](=[O:25])[C:5]3[C:6](=[CH:15][CH:2]=[CH:3][CH:4]=3)[C:7](=[O:17])[C:8]=2[CH:9]=[CH:10][CH:11]=1
Reactant: O=S(=O)(CCO)c1cccc(O)c1
Reactant: Nc1c(Br)cc(-c2ccccc2)c2c1C(=S)c1ccccc1C2=O
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 7 was repeated, except that the compounds shown in 1st and 2nd columns of the following table were used in place of the 1-amino-2-bromo-4-phenylthioanthraquinone and 3-β-hydroxyethylsulfonylphenol, respectively, thereby obtaining a corresponding anthraquinone compound. The color shade obtained by dyeing cotton with the compound is as shown in a 3rd column of the above. Each compound can exhibit superior dye performances as described hereinabove.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][C:14]2[S:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][C:5]=2[CH:4]=1.[CH3:19][C:20](=[CH2:24])[C:21](Cl)=[O:22]>C1(C)C=CC=CC=1>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:16]=[CH:15][C:14]2[S:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([C:21](=[O:22])[C:20]([CH3:24])=[CH2:19])[C:5]=2[CH:4]=1
Reactant: FC(F)(F)c1ccc2c(c1)Nc1ccccc1S2
Reactant: C=C(C)C(=O)Cl
Solvent: Cc1ccccc1
Product: C=C(C)C(=O)N1c2ccccc2Sc2ccc(C(F)(F)F)cc21
Yield: 53.1 %

Procedure:
27 g of 2-trifluoromethyl-phenothiazine and 12 g of α-methylacryloyl chloride in 100 ml of toluene were 1 for 2 hours and the mixture was evaporated to dryness. The residue was chromatographed over silica gel and elution with a 1-- 1 benzene-cyclohexane mixture gave 18 g of 2-trifluoromethyl-10-(α-methyl acryloyl)-phenothiazine in the form of white crystals melting at 103°C.
Reaction SMILES: [NH2:1][S:2]([CH2:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[C:8](OC)=[O:9])(=[O:4])=[O:3].O.[NH2:17][NH2:18]>C(O)C>[NH2:1][S:2]([CH2:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[C:8]([NH:17][NH2:18])=[O:9])(=[O:4])=[O:3]
Reactant: NN
Reactant: COC(=O)c1ccccc1CS(N)(=O)=O
Solvent: CCO
Solvent: O
Product: NNC(=O)c1ccccc1CS(N)(=O)=O
Temperature: 20 °C
Yield: 58.3 %

Procedure:
To a suspension of 84 g of methyl 2-[(aminosulfonyl)methyl]benzoate in 300 ml of absolute ethanol was added dropwise 22 g of hydrazine monohydrate. The thick suspension was heated at reflux for about 16 hours to yield a solution, then a thick suspension, at reflux temperature. The suspension was cooled to 20° C., filtered, and the residue was washed 1×100 ml of water and suction dried about three hours to provide 49 g of the subject compound; m.p. 221°-222° C.