Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[CH:13](=[N:20][O:21][CH2:22][CH2:23][OH:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O[C:26]1[CH:58]=[CH:57][C:29]([CH2:30][CH:31]2[S:35][C:34](=[O:36])[N:33]([C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]2=[O:56])=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH:13](=[N:20][O:21][CH2:22][CH2:23][O:24][C:26]1[CH:58]=[CH:57][C:29]([CH2:30][CH:31]2[S:35][C:34](=[O:36])[N:33]([C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]2=[O:56])=[CH:28][CH:27]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: OCCON=Cc1ccccc1
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1SC(Cc2ccc(OCCON=Cc3ccccc3)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 40.3 %

Procedure:
A solution of 450 mg of diethyl azodicarboxylate in 4 ml of tetrahydrofuran was added dropwise at room temperature to a solution of 383 mg of 2-(benzylideneaminooxy)ethanol (prepared as described in Preparation 1), 1.00 g of 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione and 629 mg of triphenylphosphine in 10 ml of tetrahydrofuran, and the resulting mixture was stirred at room temperature for 16 hours. At the end of this time, the reaction product was purified by column chromatography through silica gel, using a 3:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 0.53 g of the title compound as a gum.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=O)C=1.[Br:12][C:13]1[CH:14]=[N:15][C:16]2[C:17]3[N:25]([CH2:26][C:27]([CH3:30])([OH:29])[CH3:28])[C:24]([CH2:31][O:32][CH2:33][CH3:34])=[N:23][C:18]=3[CH:19]=[N:20][C:21]=2[CH:22]=1.[OH-].[NH4+:36].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:36][C:19]1[C:18]2[N:23]=[C:24]([CH2:31][O:32][CH2:33][CH3:34])[N:25]([CH2:26][C:27]([CH3:28])([OH:29])[CH3:30])[C:17]=2[C:16]2[N:15]=[CH:14][C:13]([Br:12])=[CH:22][C:21]=2[N:20]=1
Reactant: CCOCc1nc2cnc3cc(Br)cnc3c2n1CC(C)(C)O
Reactant: [NH4+]
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: CCOCc1nc2c(N)nc3cc(Br)cnc3c2n1CC(C)(C)O
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
mCPBA (35.5 g of 77% purity, 158 mmol) was added to a stirred solution of 1-[7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (15 g, 0.040 mol) in chloroform (400 mL), and the reaction was stirred at room temperature for 2.5 hours. Concentrated ammonium hydroxide (200 mL) was added, and then p-toluenesulfonyl chloride (18.9 g, 98.9 mmol) was added over a period of five minutes. The reaction mixture was stirred at room temperature for 2.5 hours, and an analysis by liquid chromatography/mass spectrometry (LC/MS) indicated the presence of starting material. Additional p-toluenesulfonyl chloride (11 g) was added, and the reaction mixture was stirred at room temperature for one hour. An analysis by LC/MS indicated the reaction was still incomplete. Additional ammonium hydroxide (100 mL) and p-toluenesulfonyl chloride (10 g) were added, and the mixture was stirred for 30 minutes at room temperature. The aqueous layer was separated and extracted with dichloromethane (2×300 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (41.4 g) was purified by automated flash chromatography (FLASH 65I cartridge, eluting with ethyl acetate:methanol in a gradient from 97:3 to 85:15) to provide 5.96 g of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a yellow solid.
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2.[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:17][CH:16]=1.[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33].CO>C(OCC)(=O)C>[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33].[NH:10]1[C:11]2[C:7](=[C:6]([O:5][CH2:4][C@@H:2]([OH:1])[CH2:3][N:28]3[CH2:29][CH2:30][N:25]([C:18]4[C:19]5[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=5)[N:15]=[CH:16][CH:17]=4)[CH2:26][CH2:27]3)[CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Reactant: c1ccc2c(N3CCNCC3)ccnc2c1
Agent: O=C(O)C(=O)O
Solvent: CO
Solvent: CCOC(C)=O
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CCN(c2ccnc3ccccc23)CC1

Procedure:
The title compound was prepared in similar fashion from (S)-(+)-4-(oxiranylmethoxy)-1H-indole and 1-(4-quinolinyl)piperazine. The resulting free base was dissolved in ethyl acetate, and precipitated with one equivalent of oxalic acid in ethyl acetate in 64% overall yield. mp 150°-151°. FDMS m/e=402 (M+ of free base). α[D]589 =-12.41 (c=0.76, methanol).
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[CH3:20])=[C:4]([Cl:23])[CH:3]=1.[C:24](OC(=O)C)(=[O:26])[CH3:25].C(O)(=O)C>ClCCCl>[C:24]([NH:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[CH3:20])=[C:4]([Cl:23])[CH:3]=1)(=[O:26])[CH3:25]
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)c1ccc2nc(C)n(Cc3ccc(N)cc3Cl)c2n1
Solvent: ClCCCl
Solvent: CC(=O)O
Product: COC(=O)c1ccc2nc(C)n(Cc3ccc(NC(C)=O)cc3Cl)c2n1
Yield: 82.2 %

Procedure:
Methyl 3-(4-amino-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylate (150 mg) was dissolved in 1,2-dichloroethane (1.5 ml), and acetic anhydride (148 mg) and acetic acid (87 mg) were added at room temperature. The mixture was refluxed under heating for 1 hr. The reaction mixture was concentrated under reduced pressure, and ice water, a saturated aqueous sodium hydrogencarbonate solution were successively added to the residue. The precipitated white crystals were collected by filtration, washed with water, and dried under reduced pressure to give the objective compound (139 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:16]=[C:15]([CH2:17][C:18]([NH:20][C@H:21]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH2:22][CH:23]([CH3:25])[CH3:24])=[O:19])[CH:14]=[CH:13][C:5]=1[C:6]([O:8]C(C)(C)C)=[O:7])[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:16]=[C:15]([CH2:17][C:18]([NH:20][C@H:21]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[N:32]2[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]2)[CH2:22][CH:23]([CH3:25])[CH3:24])=[O:19])[CH:14]=[CH:13][C:5]=1[C:6]([OH:8])=[O:7])[CH3:2]
Reactant: CCOc1cc(CC(=O)N[C@@H](CC(C)C)c2ccccc2N2CCCCC2)ccc1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOc1cc(CC(=O)N[C@@H](CC(C)C)c2ccccc2N2CCCCC2)ccc1C(=O)O

Procedure:
200 mg (0.395 mMol) of tert.butyl (S)-2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl]-benzoate (melting point: 122-123° C.; [α]D20 =+8.7°; c=1 in methanol) are stirred into 2 ml of methylene chloride together with 0.45 g (3.95 mMol) of trifluoroacetic acid overnight at ambient temperature. The mixture is evaporated down in vacuo and the evaporation residue is distributed between aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic extract is dried, filtered and evaporated down in vacuo. The evaporation residue is crystallised from ethanol/water (2/1).
Reaction SMILES: [C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.[NH2:15][CH:16]1[CH:21]2[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]2)[CH2:17]1.O>C1(C)C=CC=CC=1>[C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH:7]=[N:15][CH:16]2[CH:21]3[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]3)[CH2:17]2)=[CH:3][CH:2]=1
Reactant: O=Cc1ccc(-c2ccccc2)cc1
Reactant: NC1CN2CCC1CC2
Solvent: O
Solvent: Cc1ccccc1
Product: C(=NC1CN2CCC1CC2)c1ccc(-c2ccccc2)cc1
Yield: 59.3 %

Procedure:
4-Biphenylcarboxaldehyde (160 mg) and 3-aminoquinuclidine (110 mg) were heated under reflux in toluene (50 ml) for 2 hours using a Dean and Stark water separator. The toluene was evaporated and the residue was purified by medium pressure column chromatography on alumina (ICN Alumina N 32-63), eluting with ethyl acetate to give 3-[(biphenyl-4-ylmethylene)amino]quinuclidine (150 mg) as a colourless solid, m.p. 82°-84° C.; microanalysis, found: C, 82.2; H, 7.7; N, 9.6%; C20H22N2 requires: C, 82.7; H, 7.6; N, 9.6%; NMR (CDCl3): 1.35-1.5(1H, m), 1.6-1.8(3H, m), 2.2-2.3(1H, m), 2.8-3.0(4H, m), 3.0-3.2(2H, m), 3.4-3.5(1H, m), 7.3-7.5(3H, m), 7.55-7.65(4H, m), 7.8(2H, dd) and 8.3(1H, s); m/z 291 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:8]=1)[NH2:5].Cl[C:19]1[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=1.O1CCOCC1.CS(O)(=O)=O>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:6]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:8]=1
Reactant: CC1(C)OB(c2cc(N)cc(F)c2)OC1(C)C
Reactant: FC(F)(F)c1ccnc(Cl)n1
Agent: CS(=O)(=O)O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CC1(C)OB(c2cc(F)cc(Nc3nccc(C(F)(F)F)n3)c2)OC1(C)C
Temperature: 100 °C
Yield: 76.4 %

Procedure:
To a flask containing 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.3 g, 14.00 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (2.94 g, 16.10 mmol) were added dioxane (44 mL) and methanesulfonic acid (1.55 g, 16.10 mmol) and the reaction was heated at 100° C. overnight. The reaction was cooled, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield. N-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (4.10 g, 10.70 mmol, 76% yield). MS ESI: [M+H]+ m/z 384. 1H NMR (500 MHz, DMSO-d6) δ 10.41 (s, 1H), 8.85 (d, J=4.9, 1H), 7.92 (dt, J=2.3, 12.1, 1H), 7.77 (d, J=1.5, 1H), 7.32 (d, J=4.9, 1H), 6.98 (dd, J=2.2, 8.4, 1H), 1.28 (s, 12H).
Reaction SMILES: [F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:40]=[CH:41][CH:42]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=2)[C:34]([OH:36])=O)=[O:30])[CH:11]=1)=[O:9].C(N(C(C)C)CC)(C)C.[CH2:54]([NH:56][CH2:57][CH2:58][N:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1)[CH3:55].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:54]([N:56]([CH2:57][CH2:58][N:59]1[CH2:60][CH2:61][O:62][CH2:63][CH2:64]1)[C:34](=[O:36])[C:33]1[CH:37]=[CH:38][CH:39]=[C:31]([C:29]([NH:28][C:17]2[CH:18]=[CH:19][C:20]([N:22]3[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]3)=[CH:21][C:16]=2[C:12]2[CH:11]=[C:10]([C:8](=[O:9])[NH:7][CH2:6][C:5]3[CH:40]=[CH:41][CH:42]=[C:3]([C:2]([F:43])([F:44])[F:1])[CH:4]=3)[CH:15]=[CH:14][N:13]=2)=[O:30])[CH:32]=1)[CH3:55]
Reactant: CCNCCN1CCOCC1
Reactant: O=C(O)c1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCN(CCN1CCOCC1)C(=O)c1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 25 mg of 3-((4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzoic acid 4.1e, 17 mg of diisopropylethylamine and 9 mg of N-ethyl-2-morpholinoethanamine in 1 mL of DMF was added 17 mg of HATU. The mixture was stirred at 25° C. for 1 h. The solution was injected onto a preparative reverse phase HPLC and the product was eluted with 0.5% TFA in a gradient of water and acetonitrile. The yield was 11.2 mg of product. 1H-NMR (400 MHz, DMSO-d6, ppm) δ 12.46 (s, 1H), 9.90 (s, 1H), 9.57 (t, J=6.1 Hz, 1H), 8.90 (d, J=5.1 Hz, 1H), 8.36, (s, 2H), 8.03-7.92 (m, 2H), 7.87 (dd, J=5.1, 1.3 Hz, 1H), 7.75-7.53 (m, 26H), 7.39 (s, 1H), 4.63 (d, J=5.8 Hz, 2H), 4.03 (s, 2H), 3.82 (s, 2H), 3.60 (s, 4H), 3.40 (d, J=23.1 Hz, 6H), 3.24 (s, 4H), 1.77 (s, 4H), 1.61 (s, 2H), 1.08 (t, J=6.5 Hz, 10H). MS (ES, m/z): 743 [M+H]+.
Reaction SMILES: [C:1](=[O:25])([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[O:2][CH:3](Cl)[CH3:4].[C:26]([NH:29][C:30]1[C:31]([I:46])=[C:32]([N:41]([CH3:45])[C:42](=[O:44])[CH3:43])[C:33]([I:40])=[C:34]([C:37]([O-:39])=[O:38])[C:35]=1[I:36])(=[O:28])[CH3:27].[K+].[I-].[K+]>CN(C)C=O>[C:26]([NH:29][C:30]1[C:31]([I:46])=[C:32]([N:41]([CH3:45])[C:42](=[O:44])[CH3:43])[C:33]([I:40])=[C:34]([C:37]([O:39][CH:3]([O:2][C:1]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[O:25])[CH3:4])=[O:38])[C:35]=1[I:36])(=[O:28])[CH3:27]
Reactant: CC(=O)Nc1c(I)c(C(=O)[O-])c(I)c(N(C)C(C)=O)c1I
Reactant: CCCCCCCCCCCCCCCCCCOC(=O)OC(C)Cl
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCOC(=O)OC(C)OC(=O)c1c(I)c(NC(C)=O)c(I)c(N(C)C(C)=O)c1I
Temperature: 50 °C
Reaction time: 18 h

Procedure:
1-Chloroethyl octadecyl carbonate (7.54 g, 20 mmol) was added at room temperature to a solution of potassium 5-acetamido-3-(N-methylacetamido)-2,4,6-triiodobenzenecarboxylate (15.99 g, 24 mmol) and potassium iodide (0.33 g, 2 mmol) in dry N,N-dimethylformamide. After stirring at 50° C. for 18 hours the solvent was removed at reduced pressure. The residue was suspended in chloroform (200 ml) and washed three times with a saturated sodium bicarbonate solution and finally twice with water. After drying with magnesium sulphate the solvent was removed at reduced pressure. Yield: 18.6 g. The product was further purified by flash chromatography (Silicagel 60, chloroform/acetonitrile 85:15). 1H NMR (DMSO-d6): δ 0.852(CH2CH3), 1.236(CH2), 1.639(CHCH3),1.657(COOCH2CH2), 1.670(N(CH3)COCH3), 2.051(NCOCH3),2.965(NCH3), 4.154(COOCH2), 6.971 (CHCH3),10.103 (NH).
Reaction SMILES: O.[NH2:2][NH2:3].Cl[C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH2:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[N+:15]([O-:17])=[O:16]>C(O)C>[N+:15]([C:6]1[CH:7]=[C:8]([S:11](=[O:13])(=[O:12])[NH2:14])[CH:9]=[CH:10][C:5]=1[NH:2][NH2:3])([O-:17])=[O:16]
Reactant: NS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: NN
Solvent: CCO
Solvent: O
Product: NNc1ccc(S(N)(=O)=O)cc1[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 93.4 %

Procedure:
20 ml of hydrazine hydrate were added to a suspension of 47.33 g of 4-chloro-3-nitrobenzenesulfonamide [prepared as described in: J. Am. Chem. Soc. 73, 2558 (1951)] in 200 ml of abs. ethanol. The mixture was boiled under stirring for 30 minutes, then cooled down. The crystals were filtered by suction and thoroughly washed with water to obtain 43.38 g (93.4%) of 2-nitro-4-sulfamoylphenylhydrazine, m.p.: 217°-218° C. (with decomposition).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([OH:23])[C@@H:12]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:11][C@H:10]1[N:33]=[N+]=[N-])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(S)CCS.C(N(CC)CC)C>CO>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([OH:23])[C@@H:12]([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:11][C@H:10]1[NH2:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=N[C@@H]1O[C@H](COCc2ccccc2)[C@H](O)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: SCCCS
Solvent: CO
Solvent: CCN(CC)CC
Product: N[C@@H]1O[C@H](COCc2ccccc2)[C@H](O)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 93.8 %

Procedure:
A mixture of 2,3,6-tri-O-benzyl-β-D-galactopyranosyl azide (3.00 g, 6.31 mmol), propane-1,3-dithiol (3.40 g, 31.50 mmol), and triethylamine (3.50 g, 31.5 mmol) in MeOH (31 ml) was stirred under nitrogen at room temperature for 10 hours. The reaction mixture was evaporated and purified by chromatography using CHC3/EtOH 10:0.3 v/v to give 2,3,6-tri-O-benzyl-β-D-galactopyranosyl amine (2.66 g, 94%);
Reaction SMILES: N[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[C:9]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:7][CH:6]=2.[OH:15]S(O)(=O)=O.N([O-])=O.[Na+]>O>[OH:15][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[C:9]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:7][CH:6]=2
Reactant: O=S(=O)(O)O
Reactant: Nc1cnc2cccc([N+](=O)[O-])c2c1
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=[N+]([O-])c1cccc2ncc(O)cc12
Temperature: 5 °C
Reaction time: 0.75 h

Procedure:
3-Amino-5-nitroquinoline, as described above in Step C, (4.48 g, 23.68 mmol) was dissolved in H2SO4 (6N aqueous solution, 50 mL, 300 mmol) and cooled to approximately 5° C. A 0° C. solution of NaNO2 (1.63g, 23.68 mmol) in water (5 mL) was added dropwise to the amine solution. After 45 min at 5 to 10° C., the reaction was poured into refluxing 5% aqueous H2SO4 (300 mL). The resulting mixture was heated for 5 min, then cooled and extracted once with CH2Cl2. The aqueous layer was basified with solid NaHCO3 and extracted once with CH2Cl2. The aqueous layer was then neutralized with aqueous HCl and filtered. The filtered solid was dried in vacuo to yield the above-titled compound.
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][CH:7]([CH:9]1[CH2:14][CH2:13][C:12]([CH3:15])=[CH:11][CH2:10]1)[CH3:8])(=[O:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:24])C=1>C(Cl)Cl>[C:1]([O:4][CH2:5][CH2:6][CH:7]([CH:9]1[CH2:14][CH2:13][C:12]2([O:24][CH:11]2[CH2:10]1)[CH3:15])[CH3:8])(=[O:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)OCCC(C)C1CC=C(C)CC1
Solvent: ClCCl
Product: CC(=O)OCCC(C)C1CCC2(C)OC2C1

Procedure:
The procedure of Example 1 was followed for the epoxidation of 4.2g (0.02 mole) of acetic acid, 3-(4-methyl-3-cyclohexenyl)butyl ester using 4.1g (0.02 mole) of 85% m-chloroperbenzoic acid in 150 ml of methylene chloride. Obtained was 4.1g of pure acetic acid, 3-(3,4-epoxy-4-methylcyclohexyl) butyl ester as a clear, colorless liquid. (See Table I).
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[CH:10]=[C:9]([CH3:14])[C:8]=1[CH3:15])[CH3:2].N1C=CC=CC=1.[Br:22]Br>ClCCl>[Br:22][C:10]1[C:9]([CH3:14])=[C:8]([CH3:15])[C:7]([O:6][CH2:5][CH2:4][O:3][CH2:1][CH3:2])=[CH:12][C:11]=1[CH3:13]
Reactant: CCOCCOc1cc(C)cc(C)c1C
Reactant: BrBr
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOCCOc1cc(C)c(Br)c(C)c1C
Temperature: 0 °C
Yield: 102.4 %

Procedure:
To a mixture of 1-(2-ethoxyethoxy)-2,3,5-trimethylbenzene (1.0 g, 4.08 mmol), pyridine (0.097 mL, 1.20 mmol) and dichloromethane (10 mL) was added a solution of bromine (0.66 g, 4.12 mmol) in dichloromethane (1 mL) under stirring at 0° C., and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=49/1-hexane/ethyl acetate=4/1) to give the title compound (1.2 g, yield 99%) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([S:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[NH:15][NH2:16].C(O[CH:20](O)[C:21]([F:24])([F:23])[F:22])C.CS(O)(=O)=O>C(O)C>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([S:9][CH2:10][C:11]([F:13])([F:14])[F:12])=[CH:4][C:3]=1[NH:15][N:16]=[CH:20][C:21]([F:24])([F:23])[F:22]
Reactant: CCOC(O)C(F)(F)F
Reactant: Cc1cc(F)c(NN)cc1SCC(F)(F)F
Agent: CS(=O)(=O)O
Solvent: CCO
Product: Cc1cc(F)c(NN=CC(F)(F)F)cc1SCC(F)(F)F
Temperature: 25 °C
Yield: 90.8 %

Procedure:
A mixture of 3.1 g of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenylhydrazine, 1.9 g of trifluoroacetaldehyde ethyl hemiacetal, 0.5 g of methanesulfonic acid and 100 ml of ethanol was refluxed with heating for 5 hours. After the reaction mixture was cooled to room temperature, it was concentrated under reduced pressure and extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 3.7 g of trifluoroacetaldehyde {2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}hydrazone.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]([F:10])([F:9])[F:8])=[N:4][CH:3]=1.[Br:11]N1C(=O)CCC1=O>C1C=CC=CC=1>[Br:11][CH2:1][C:2]1[S:6][C:5]([C:7]([F:10])([F:9])[F:8])=[N:4][CH:3]=1
Reactant: Cc1cnc(C(F)(F)F)s1
Reactant: O=C1CCC(=O)N1Br
Solvent: c1ccccc1
Product: FC(F)(F)c1ncc(CBr)s1
Reaction time: 0.5 h
Yield: 73 %

Procedure:
5-Methyl-2-trifluoromethylthiazole (2.26 g, 13.5 mmol), N-bromosuccinimide (2.64 g, 14.6 mmol), and 50 mL of benzene were placed in a jacketed flask and the resulting mixture was stirred and irradiated with a 250 Watt sun lamp placed 10 cm from the flask. The temperature rose from 25° to 40° C. After 3 hr an additional 0.26 g (1.5 mmol) of N-bromosuccinimide was added and the reaction continued another 30 min. Analysis of an aliquot by gas-liquid chromatography indicated that the mixture contained about 7 percent starting material, 73 percent title compound, and 17 percent dibrominated material. The mixture was extracted with 50 mL of 2 percent aqueous sodium hydroxide, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain a yellow oil. This was purified by medium pressure liquid chromatography to obtain 1.86 g (56 percent of theory) of 5-bromomethyl-2-trifluoromethylthiazole as a pale yellow oil which was 97 percent pure by gas liquid chromatography. The proton NMR spectrum had absorptions at δ4.69 (s, 2H) and 7.87 (s, 1H).
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[S:10][C:5]=2[C:4](=[O:17])[N:3]1[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.Cl[CH2:32][C:33]#[N:34].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:33]([CH2:32][N:7]1[C:6]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[S:10][C:5]=2[C:4](=[O:17])[N:3]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[C:2]1=[O:1])#[N:34]
Reactant: N#CCCl
Reactant: CC(C)(C)OC(=O)N1CCC(n2c(=O)[nH]c3cc(-c4ccccc4)sc3c2=O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(n2c(=O)c3sc(-c4ccccc4)cc3n(CC#N)c2=O)CC1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
To a solution of tert-butyl 4-(2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate (5 g; compound B50) and chloroacetonitrile (883 mg) in DMF (45 ml) is added potassium carbonate (1.62 g). The mixture is stirred for 1 h at 100° C. and then poured into ice-cold water. The resulting precipitate is filtered off, washed with water and dried under reduced pressure to give tert-butyl 4-[1-(cyanomethyl)-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate (compound B14a) as a solid, which is used without further purification for the next step.