Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCOCC.[CH3:6][CH:7]([C:9]1[C:10]([O:28][Si](C)(C)C)(C#N)[CH2:11][C:12]([CH3:25])=[CH:13][CH2:14][CH2:15][C:16]([CH3:24])=[CH:17][CH2:18][CH2:19][C:20]([CH3:23])=[CH:21][CH:22]=1)[CH3:8].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:8][CH:7]([C:9]1[C:10](=[O:28])[CH2:11][C:12]([CH3:25])=[CH:13][CH2:14][CH2:15][C:16]([CH3:24])=[CH:17][CH2:18][CH2:19][C:20]([CH3:23])=[CH:21][CH:22]=1)[CH3:6]
Reactant: CC1=CC=C(C(C)C)C(C#N)(O[Si](C)(C)C)CC(C)=CCCC(C)=CCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1=CC=C(C(C)C)C(=O)CC(C)=CCCC(C)=CCC1
Reaction time: 48 h
Yield: 84.4 %

Procedure:
The above cyanohydrine trimethylsily ether compound, 2-(1-methylethyl)-5,9,13-trimethyl-1-trimethylsiloxy-2,4,8,12-cyclotetradecatetraen-1-carbonitrile (657 mg, 1.7 mmol) was dissolved in 10% aqueous tetrahydrofuran (10 ml). To the solution on an ice-water bath was added a solution of 1M tetra n-butylammonium fluoride in tetrahydrofuran (0.02 ml), and the mixture was stirred and then allowed to stand at room temperature for 2 days. Most of the tetrahydrofuran was removed in vacuo and the residue was dissolved in ethyl ether. The ether layer was dried over MgSO4, filtered, concentrated, and subjected to silica gel column chromatography (solvent: n-hexane/ethyl acetate=30:1) to obtain the ketone compound, 2-(1-methylethyl)-5,9,13-trimethyl-2,4,8,12-cyclotetradecatetraen-1-one (411 mg, 85%).
Reaction SMILES: [CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=O)[CH:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].[NH2:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([OH:39])[CH2:35][CH2:34]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[CH2:1]([S:3]([N:6]1[CH2:7][CH2:8][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][NH:32][C@H:33]5[CH2:38][CH2:37][C@H:36]([OH:39])[CH2:35][CH2:34]5)[CH:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:10][CH2:11]1)(=[O:5])=[O:4])[CH3:2]
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(C=O)c4)cc23)CC1
Reactant: N[C@H]1CC[C@H](O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(CN[C@H]5CC[C@H](O)CC5)c4)cc23)CC1

Procedure:
Following the general procedure of example 16, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (50 mg, 0.114 mmol), trans-4-aminocyclohexanol (10 mg, 0.087 mmol) and NaBH(OAc)3 (58 mg, 0.261 mmol) were reacted to give the title compound (6.0 mg, 9.8%).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][CH2:28][CH:29]([C:31]1[C:32]([Cl:37])=[N:33][CH:34]=[CH:35][CH:36]=1)[OH:30])(C(C)(C)C)(C)C>C1COCC1>[Cl:37][C:32]1[C:31]([CH:29]([OH:30])[CH2:28][CH2:27][OH:26])=[CH:36][CH:35]=[CH:34][N:33]=1
Reactant: CC(C)(C)[Si](C)(C)OCCC(O)c1cccnc1Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: OCCC(O)c1cccnc1Cl
Reaction time: 1 h

Procedure:
A solution of tetrabutylammonium fluoride in THF (1M, 3.3 mL) was added to a solution of 3-(tert-butyldimethylsilyloxy)-1-(2-chloropyridin-3-yl)propan-1-ol in THF (5 mL) and stirred for 60 min, then silica gel was added and the solvent were removed under reduced pressure. The entire flask contents were added to a column, that was prepared and eluted with 75% ETOAC/Hex, to yield that titled product (0.49 g), NMR CD3OD 1H δ 8.3 (dd, 1H), 8.0 (dd, 1H), 7.4 (dd, 1H), 5.1 (dd, 1H), 3.8 (m, 2H), 2.0 (m, 1H), 1.8 (m, 1H); MH+=188/190.
Reaction SMILES: [ClH:1].[CH3:2][N:3]1[C:7]2[CH2:8][CH2:9][N:10](C(OC(C)(C)C)=O)[CH2:11][CH2:12][C:6]=2[C:5]2[CH:20]=[CH:21][C:22]([N:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=4)=[CH:26][C:25]3=[O:40])=[N:23][C:4]1=2>CO.CCOCC>[ClH:1].[CH3:2][N:3]1[C:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH2:12][C:6]=2[C:5]2[CH:20]=[CH:21][C:22]([N:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=4)=[CH:26][C:25]3=[O:40])=[N:23][C:4]1=2
Reactant: Cn1c2c(c3ccc(-n4ccc(-c5ccc(C(F)(F)F)nc5)cc4=O)nc31)CCN(C(=O)OC(C)(C)C)CC2
Agent: Cl
Solvent: CCOCC
Solvent: CO
Product: Cn1c2c(c3ccc(-n4ccc(-c5ccc(C(F)(F)F)nc5)cc4=O)nc31)CCNCC2
Temperature: 25 °C
Reaction time: 18 h
Yield: 76 %

Procedure:
1.25 M HCl in MeOH (3.2 mL) was added to tert-butyl 10-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-1(2H)-yl)-5,8,9,10-tetrahydropyrido[3′,2′:4,5]pyrrolo[2,3-d]azepine-7(6H)-carboxylate (55 mg, 0.10 mmol), and the resulting solution was stirred under N2 at ambient temperature for 18 h. The solution was diluted with MeOH (2.2 mL) and Et2O (25 mL), and the resulting solids were collected by filtration to provide the title compound (37 mg, 76%) as a yellow powder: mp 320-325° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.28 (s, 2H), 9.21 (d, J=2.0 Hz, 1H), 8.50 (dd, J=8.5, 2.0 Hz, 1H), 8.10-8.04 (m, 3H), 7.41 (d, J=8.0 Hz, 2H), 7.03 (d, J=1.5 Hz, 1H), 6.85 (dd, J=7.5, 3.5 Hz, 1H), 5.98 (d, J=2.5 Hz, 1H), 3.76 (s, 3H), 3.41-3.40 (m, 2H), 3.33-3.31 (m, 2H, overlaps with solvent), 3.17 (t, J=5.5 Hz, 2H); ESI MS m/z 440 [M+H]+; HPLC (Method A) 99.0% (AUC), tR=13.6 min.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:28][CH3:29])[C:4]1[CH:5]=[C:6]([C:13](N2CCOCC2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)C#N)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11].CC(O)=[O:32]>>[CH3:1][O:2][CH:3]([O:28][CH3:29])[C:4]1[CH:5]=[C:6]([C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:32])[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11]
Reactant: COC(OC)c1cc(C(C#N)(c2ccccc2)N2CCOCC2)ccc1[N+](=O)[O-]
Reactant: CC(=O)O
Product: COC(OC)c1cc(C(=O)c2ccccc2)ccc1[N+](=O)[O-]

Procedure:
(3-Dimethoxymethyl-4-nitro-phenyl)-morpholin-4-yl-phenyl-acetonitrile (0.7 mol) in CH3CO2H (1500 ml) was stirred and refluxed for 30 min. The mixture was poured on ice/water and extracted with diisopropyl ether. The organic layer was washed with alkalic water and water. The organic layer was dried (MgSO4) and evaporated to yield a residue. The aqueous layers which contained product were extracted with CH2Cl2. The organic layer was dried (MgSO4) and evaporated to yield a residue. The combined residues were purified on a glass filter over silica gel (eluent: CH2Cl2). The pure fractions were collected and evaporated to yield the title compound as a residue.
Reaction SMILES: [H-].[Na+].[C:3]1([CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1COCC1>[C:3]1([CH:9]([CH2:10][O:11][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:12][OH:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: OCC(CO)c1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC(CO)c1ccccc1
Reaction time: 0.75 h

Procedure:
Sodium hydride (60% dispersion in mineral oil, 525 mg, 13 mmol) was added to a round bottom flask and washed with 3×5 mL of dry hexane. Dry THF (25 mL) was then added, followed by 2-phenyl-1,3-propanediol (2.0 g, 13 mmol). Another 25 mL of dry THF was added to facilitate stirring of the resulting thick suspension. After 45 min., tert-butyldimethylsilyl chloride was added in one portion. After stirring for 2 h, the mixture was partitioned between 100 mL of ethyl ether and 60 mL of 10% aqueous potassium carbonate. The aqueous layer was extracted with 2×30 mL of ethyl ether. The combined organic layers were washed with 40 mL of brine, dried over sodium sulfate, and evaporated. Purification by flash column chromatography, eluting with 10% ethyl acetate in hexane, gave the 3.36 g of the title compound as a colorless liquid. 1NMR (400 MHz,CD3OD): δ 7.30-7.16(m, 5H), 3.90 (dd, 1H, J=11, 7 Hz), 3.88 (dd, 1H, J=10, 6 Hz), 3.83 (dd, 1H, J=10, 6 Hz), 3.76 (dd, 1H, J=11, 7 Hz), 2.91 (quintet, 1H, J=6 Hz), 0.84 (s, 9H),-0.04 (s, 3H),-0.05 (s, 3H). Mass spectrum (NH3 /CI): m/z=267 (M+1).
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH2:12])[CH:7]=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[CH3:3][O:4][C:5](=[O:13])[C:6]1[C:11]([Br:1])=[CH:10][N:9]=[C:8]([NH2:12])[CH:7]=1
Reactant: BrBr
Reactant: COC(=O)c1ccnc(N)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: COC(=O)c1cc(N)ncc1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 23 %

Procedure:
Bromine (1.78 ml, 34.8 mmol) was added dropwise over an hour to a stirred solution of 2-amino-isonicotinic acid methyl ester (5.13 g, 33.75 mmol) in chloroform (350 ml) at room temperature and the orange solution stirred at room temperature overnight. A 2N solution of sodium thiosulfate (300 ml) was added to the reaction and stirred for ten minutes. The two layers were separated and the aqueous extracted with chloroform (100 ml). The combined organics were dried (MgSO4) and concentrated under reduced pressure. The desired isomer was purified by flash column chromatography using ethyl acetate 2/3 hexane as eluent to afford 2-amino-5-bromo-isonicotinic acid methyl ester as a yellow solid (1.79 g, 23%). 1H NMR (CDCl3): 8.21 (1 H, s, py); 6.79 (1 H, s, py); 4.53 (2 H, br s, NH2); 3.88 (3 H, s, CO2CH3).
Reaction SMILES: [C:1]1([NH:7][C:8]2[C:16]3[C:15]4[CH2:17][NH:18][CH2:19][CH2:20][C:14]=4[NH:13][C:12]=3[N:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:21][C:22]1[CH:23]=[C:24]([N:28]=[C:29]=[O:30])[CH:25]=[CH:26][CH:27]=1.C(N(CC)CC)C>ClCCCl>[Cl:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]([N:18]2[CH2:19][CH2:20][C:14]3[NH:13][C:12]4[N:11]=[CH:10][CH:9]=[C:8]([NH:7][C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:16]=4[C:15]=3[CH2:17]2)=[O:30])[CH:25]=[CH:26][CH:27]=1
Reactant: O=C=Nc1cccc(Cl)c1
Reactant: c1ccc(Nc2ccnc3[nH]c4c(c23)CNCC4)cc1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1cccc(Cl)c1)N1CCc2[nH]c3nccc(Nc4ccccc4)c3c2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 25.5 %

Procedure:
Phenyl-(6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrol-4-yl)-amine (40 mg, 0.15 mmol), 3-chlorophenyl isocyanate (28 mg, 0.18 mmol), and triethylamine (0.06 mL, 0.45 mmol) were dissolved in 1,2-dichloroethane (2.0 mL), and stirred overnight at room temperature. The reaction mixture was added directly to a Biotage column. The crude product was purified via Biotage eluting with CH2Cl2/MeOH (9/1, v/v) to provide 10 (16 mg, 25% yield) as an off-white solid. LC-MS (M+H=418, obsd.=418).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]([CH2:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[C:5]2=[O:19].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][N:6]([CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[C:5]3=[O:19])=[CH:23][CH:22]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: O=c1c2cc(Br)ccc2ncn1Cc1cccnc1
Product: O=c1c2cc(Oc3ccc(Cl)cc3)ccc2ncn1Cc1cccnc1

Procedure:
The titled compound was prepared in the same manner as in Example 1 (1) c) from 6-bromo-3-(3-pyridylmethyl)-4 (3H)-quinazolinone and 4-chlorophenol.
Reaction SMILES: [CH2:1]([C:3]1[CH:15]=[CH:14][C:6]([C:7]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=O)=[CH:5][CH:4]=1)[CH3:2].C1(C)C=CC=CC=1>O.Cl.[Zn]>[CH2:1]([C:3]1[CH:15]=[CH:14][C:6]([CH2:7][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(C(=O)CCC(=O)O)cc1
Agent: Cl
Agent: [Zn]
Solvent: Cc1ccccc1
Solvent: O
Product: CCc1ccc(CCCC(=O)O)cc1

Procedure:
To a 500 mL round-bottomed flask equipped with condenser and nitrogen inlet were added 41.2 grams (200 mmol) 3-(4-ethylbenzoyl)-propionic acid, activated zinc prepared from 82.4 grams (400 mmol) mossy zinc and 8.2 grams mercuric chloride in 125 mL water and 8 mL concentrated hydrochloric acid, 77 mL water, 177 mL concentrated hydrochloric acid, and 100 mL toluene. The mixture was refluxed 60 hours with addition of two 50 mL portions of concentrated hydrochloric acid, cooled, and the layers separated. The organic layer was extracted into 3N aqueous sodium hydroxide, which was then acidified and extracted into ethyl acetate. The organic layer was dried over sodium sulfate and evaporated to afford 28.9 grams (75%), M.P. 70°-72° C.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)O1.C([O-])([O-])=O.[K+].[K+].Br[C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([N+:37]([O-:39])=[O:38])[CH:31]=1>CN(C=O)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)=[CH:31][C:32]=1[N+:37]([O-:39])=[O:38]
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: O=[N+]([O-])c1cc(Br)ccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC=C(c2ccc(F)c([N+](=O)[O-])c2)CC1
Temperature: 80 °C
Yield: 64.7 %

Procedure:
To a 150-mL RB-flask containing tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (5.58 g, 16.5 mmol), K2CO3 (5.60 g, 40.5 mmol) and PdCl2dppf (1.48 mmol, 1.21 g) was added a solution of 4-bromo-1-fluoro-2-nitrobenzene (3.30 g, 15.0 mmol) in DMF (50.0 mL) at room temperature under argon. The mixture was heated to 80° C. under argon for 12 hours. After cooling to room temperature, the mixture was filtered through Celite and the Celite was washed with EtOAc (3×100 mL). The filtrates were washed with H2O (3×200 mL), brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (EtOAc/hexanes 1:9) to afford tert-butyl 4-(4-fluoro-3-nitrophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate (3.13 g, 65.1%): 1H NMR (400 MHz, CDCl3) δ 8.06-7.89 (m, 1H), 7.66-7.49 (m, 1H), 7.30-7.10 (m, 1H), 6.19-5.95 (br, 1H), 4.10-3.95 (m, 2H), 3.58 (t, 2H, J=5.6 Hz), 2.49-2.34 (m, 2H), 1.42 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28]CC4C=CC(Cl)=CC=4Cl)[C@@H:14]([O:15]CC4C=CC(Cl)=CC=4Cl)[C@@:12]3([CH2:38][F:39])[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1>CO.ClCCl.[Pd]>[NH2:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:14]([OH:15])[C@@:12]3([CH2:38][F:39])[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2c1ccn2[C@@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)[C@]1(O)CF
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Product: Nc1ncnc2c1ccn2[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)CF
Reaction time: 12 h
Yield: 103.3 %

Procedure:
The compound from Step B (16 mg) was dissolved in 1:1 methanol/dichloromethane, 10% Pd-C was added, and the suspension stirred under an H2 atmosphere for 12 h. The catalyst was removed by filtration through a celite pad and washed with copious amounts of methanol. The combined filtrate was evaporated in vacuo and the residue was purified by flash chromatography (SiO2, 10% methanol in EtOAc containing 0.1% triethylamine) to give the title compound (8 mg) as a white powder.
Reaction SMILES: CC1(C)[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=[O:21])O1.[CH3:23][C:24]1[S:25][C:26]([S:30]([NH2:33])(=[O:32])=[O:31])=[C:27]([CH3:29])[N:28]=1>>[F:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][N:10]([O:11][CH3:12])[C:8](=[O:9])[CH:7]=[C:5]([OH:6])[C:4]([NH:33][S:30]([C:26]2[S:25][C:24]([CH3:23])=[N:28][C:27]=2[CH3:29])(=[O:31])=[O:32])=[O:21])=[CH:19][CH:18]=1
Reactant: CON(Cc1ccc(F)cc1)C(=O)C=C1OC(C)(C)OC1=O
Reactant: Cc1nc(C)c(S(N)(=O)=O)s1
Product: CON(Cc1ccc(F)cc1)C(=O)C=C(O)C(=O)NS(=O)(=O)c1sc(C)nc1C

Procedure:
2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamide was treated with 2,4-dimethyl-thiazole-5-sulfonic acid amide as described in the preparation of compound 1 to yield the title compound. 1H NMR (500 MHz, CDCl3) δ: 2.71 (s, 6), 3.63 (s, 3), 4.76 (s, 2), 6.47 (s, 1), 7.01 (m, 2), 7.26 (m, 2). 13C NMR (125 MHz, CDCl3) δ: 16.51, 19.25, 48.29, 63.20, 92.66, 115.70, 115.87, 127.43, 130.23, 130.30, 130.97, 158.92, 159.24, 159.58, 161.69, 163.66, 170.81, 172.19.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:21][C:22]1([CH3:34])[O:26][C@H:25]([CH2:27][CH2:28]OS(C)(=O)=O)[CH2:24][O:23]1>>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[N:16]([CH2:28][CH2:27][C@@H:25]3[CH2:24][O:23][C:22]([CH3:34])([CH3:21])[O:26]3)[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCN1
Reactant: CC1(C)OC[C@@H](CCOS(C)(=O)=O)O1
Product: CC1(C)OC[C@@H](CCN2CCN(C(=O)/C=C/c3ccc(Cl)c(Cl)c3)CCC2=O)O1

Procedure:
In analogy to the procedure described for example 167A, 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 1A]) and methanesulfonic acid 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl ester (prepared from 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethanol and methanesulfonyl chloride) gave after reaction at RT, the title compound as an off-white foam. MS: 441.1 (MH+, 2Cl).
Reaction SMILES: [Cl:1][C:2]1[C:11]([N+:12]([O-])=O)=[C:10]([NH:15][CH2:16][C:17]2([OH:21])[CH2:20][CH2:19][CH2:18]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1>[Pt].C(OCC)(=O)C>[NH2:12][C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([C:10]=1[NH:15][CH2:16][C:17]1([OH:21])[CH2:20][CH2:19][CH2:18]1)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: O=[N+]([O-])c1c(Cl)nc2ccccc2c1NCC1(O)CCC1
Agent: [Pt]
Solvent: CCOC(C)=O
Product: Nc1c(Cl)nc2ccccc2c1NCC1(O)CCC1

Procedure:
Platinum on carbon (0.40 g of 5%) was added to a solution of 1-{[(2-chloro-3-nitroquinolin-4-yl)amino]methyl}cyclobutanol (4.0 g, 13 mmol) in ethyl acetate (65 mL), and the mixture was placed under hydrogen pressure (40 psi, 2.8×105 Pa) on a Parr apparatus for 3.5 hours. The mixture was filtered through a layer of CELITE filter agent, and the filter cake was washed with ethyl acetate (100 mL). The filtrate was concentrated under reduced pressure to provide 1-{[(3-amino-2-chloroquinolin-4-yl)amino]methyl}cyclobutanol as a yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13]O)=[C:11]([CH3:15])[O:10][N:9]=2)=[N:6][CH:7]=1.S(Cl)([Cl:18])=O>C(Cl)Cl>[Cl:18][CH2:13][C:12]1[C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)=[N:9][O:10][C:11]=1[CH3:15]
Reactant: O=S(Cl)Cl
Reactant: Cc1onc(-c2ccc(F)cn2)c1CO
Solvent: ClCCl
Product: Cc1onc(-c2ccc(F)cn2)c1CCl
Reaction time: 0.5 h
Yield: 98.4 %

Procedure:
To a solution of [3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanol (1.0 g, 4.8 mmol) in DCM (9.6 mL) at 0° C. was added thionyl chloride (697 μL, 9.6 mmol) and the resulting mixture stirred for 30 min and then evaporated. After 1 h the reaction mixture was concentrated to give the title compound (1.07 g, 98%) as an off white solid. MS: m/e=227.2 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8]Br)=[C:6]([Br:10])[CH:5]=[CH:4][CH:3]=1.[C-:11]#[N:12].[K+]>C(O)C.O>[Br:10][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C:11]#[N:12]
Reactant: Clc1cccc(Br)c1CBr
Reactant: [C-]#N
Agent: [K+]
Solvent: O
Solvent: CCO
Product: N#CCc1c(Cl)cccc1Br
Yield: 52.3 %

Procedure:
A solution of 31.3 g of the crude 6-chloro-alpha,2-dibromotoluene in 100 ml of warm ethanol is treated with a solution of 6.7 g of potassium cyanide in 10 ml of water and the mixture is heated at reflux for 4 hours. The crude product is isolated by pouring the cooled reaction mixture into water and filtering the resulting precipitate. Recrystallization of this solid from aqueous ethanol then gives 12.4 g of 2-bromo-6-chlorophenylacetonitrile, mp 82°-84° C.
Reaction SMILES: Cl.[C:2]([CH:5]([C:13]1[C:18]([Cl:19])=[CH:17][C:16]([C:20]([F:23])([F:22])[F:21])=[CH:15][N:14]=1)[C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)(=[O:4])N.[CH3:24][OH:25]>>[Cl:19][C:18]1[C:13]([CH:5]([C:6]2[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=2)[C:2]([O:25][CH3:24])=[O:4])=[N:14][CH:15]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:17]=1
Reactant: CO
Reactant: NC(=O)C(c1ccc(Cl)cc1)c1ncc(C(F)(F)F)cc1Cl
Agent: Cl
Product: COC(=O)C(c1ccc(Cl)cc1)c1ncc(C(F)(F)F)cc1Cl
Reaction time: 16 h

Procedure:
Hydrogen chloride gas was introduced into a solution of 3.0 g of 2-[1-carbamoyl-1-(4-chlorophenyl)methyl]-3-chloro-5-trifluoromethylpyridine (prepared by the method of Example 3) in 100 ml of anhydrous methanol for 5 hours. The mixture was subsequently stirred for another 16 hours and excess hydrogen chloride was removed by passing nitrogen through the mixture. The methanol was separated off and the crude product was purified by silica gel chromatography (eluent: cyclohexane/tert-butyl methyl ether 50:1). Yield: 1.3 g (42%) of colorless crystals; mp.: 103-104° C.
Reaction SMILES: [OH:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([I:13])=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:14].C(N(CC)CC)C.[S:22]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23]1>C(#N)C>[S:22]1[CH:26]=[CH:25][C:24]([S:27]([O:1][C:2]2[C:10]([O:11][CH3:12])=[CH:9][C:8]([I:13])=[C:7]3[C:3]=2[CH2:4][NH:5][C:6]3=[O:14])(=[O:29])=[O:28])=[CH:23]1
Reactant: COc1cc(I)c2c(c1O)CNC2=O
Reactant: O=S(=O)(Cl)c1ccsc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1cc(I)c2c(c1OS(=O)(=O)c1ccsc1)CNC2=O
Yield: 80.6 %

Procedure:
In a similar manner to Step 1 of Example 227, 4-hydroxy-5-methoxy-7-iodoisoindolinone (0.265 g, 0.869 mmol) was dissolved in acetonitrile (8.0 mL), and the solution was treated with triethylamine (0.242 mL, 1.74 mmol) and 3-thiophenesulfonyl chloride (0.191 g, 1.04 mmol) to obtain 4-(3-thiophenesulfonyloxy)-5-methoxy-7-iodoisoindolinone (0.316 g, yield 81%).
Reaction SMILES: [N+]([CH2:4][C@H:5]([C@@H:7]([C@H:9]([C@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8])[OH:6])([O-])=O.[OH-].[Na+].S(=O)(=O)(O)[OH:18].[OH-].[Ba+2].[OH-]>O>[O:18]=[CH:4][C@H:5]([C@@H:7]([C@H:9]([C@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8])[OH:6]
Reactant: O=[N+]([O-])C[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO
Reactant: O=S(=O)(O)O
Agent: [Ba+2]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO

Procedure:
A solution of 5 grams of 1-deoxy-1-nitro-L-glucitol dissolved in 15 ml. of 2N sodium hydroxide was added dropwise to a stirred solution of 7.5 ml. of sulfuric acid in 9 ml. of water at room temperature. After dilution with 200 ml. of water, the solution was neutralized to Congo red indicator with warm barium hydroxide solution and the remaining sulfate ion precipitated with barium acetate solution. The barium sulfate was removed by filtration and the filtrate de-ionized by passage through 50 ml. of Dowex-50(H+) resin. The effluent and washings were concentrated at reduced pressure to a syrup. This syrup was diluted with a few drops of ethanol and allowed to crystallize. The resulting β-L-glucose was filtered with the aid of ethanol; yield 2.5 grams, mp 146°-147° C.