Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:19]=[C:20]1[CH:27]2[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:29][CH:21]1[CH2:22]3)[CH2:26]2.[OH-].[Na+]>C1(C)C=CC=CC=1>[C:1]([O:6][C:20]1([CH3:19])[CH:21]2[CH2:29][CH:25]3[CH2:24][CH:23]([CH2:28][CH:27]1[CH2:26]3)[CH2:22]2)(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C1C2CC3CC(C2)CC1C3
Reactant: C=C(C)C(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: C=C(C)C(=O)OC1(C)C2CC3CC(C2)CC1C3
Temperature: 5 °C
Reaction time: 5 h
Yield: 90.8 %

Procedure:
A 500 ml flask was flushed with nitrogen to displace the air with nitrogen, and was charged with 43.0 g (0.50 mol) of methacrylic acid, 0.95 g (5 mmol) of p-toluenesulfonic acid monohydrate (supplied by Wako Pure Chem. Ind. Ltd.) and 100 g of toluene. Separately 74.0 g (0.50 mol) of 2-methyleneadamantane, prepared by the same procedures as described in Reference Example 1, was dissolved in 100 g of toluene. The obtained solution of 2-methyleneadamantane in toluene was dropwise added to the content in the flask over a period of about 3 hours, while the content was maintained at a reaction temperature of about 5° C. Then the content was stirred for 5 hours at the same temperature. After completion of the reaction, the residual catalyst was neutralized by adding 40.0 g (50 mmol) of a 5% aqueous sodium hydroxide solution, and the neutralized liquid was washed with an aqueous saturated sodium chloride solution. The thus-obtained organic phase was subjected to column chromatography, and further, analyzed by NMR and mass spectrometry. Thus, 106.2 g (yield: 90.8%) of the object 2-methyl-2-adamantyl methacrylate was obtained.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[C:10]([NH2:19])[C:9]=2[N:8]=[CH:7]1.Cl.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>>[NH2:19][C:10]1[C:9]2[N:8]=[CH:7][N:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:21](=[O:28])[C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1
Reactant: O=C(Cl)c1ccncc1
Reactant: NCCCCn1cnc2c(N)nc3ccccc3c21
Agent: Cl
Product: Nc1nc2ccccc2c2c1ncn2CCCCNC(=O)c1ccncc1

Procedure:
According to the general method of Example 14, 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine and isonicotinoyl chloride hydrochloride were combined to provide N4-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]isonicotinamide as a white crystalline solid, m.p. 213.0-213.7° C. 1H NMR (300 MHz, DMSO-d6) δ 8.76 (m, 1H), 8.69 (d, J=5.6 Hz, 2H), 8.22 (s, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.67 (d, J=5.7 Hz, 2H), 7.62 (d, J=8.2 Hz, 1H), 7.43 (t, J=7.5 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 6.62 (broad s, 2H), 4.64 (t, J=6.8 Hz, 2H), 3.30 (m, 2H), 1.92 (m, 2H), 1.58 (m, 2H); MS (EI) m/e 360.1699 (360.1699 calcd for C20H20N6O).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[Br:9].[C:10]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[Br:9][C:3]1[C:2]([NH2:1])=[N:7][C:6]([O:8][CH3:10])=[CH:5][CH:4]=1
Reactant: Nc1nc(O)ccc1Br
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1ccc(Br)c(N)n1
Reaction time: 4 h
Yield: 12.1 %

Procedure:
Under an argon atmosphere 6-amino-5-bromo-pyridin-2-ol (23 g, 122 mmol) was dissolved in DMF (300 mL). K2CO3 (50.6 g, 366 mmol) was added followed by the addition of methyl iodide (11.4 mL, 183 mmol). The mixture was stirred for 4 h while keeping the temperature at 20-25° C. The suspension was poured onto H2O (1 L) and the aqueous phase was extracted with EtOAc (×2). The combined organic phases washed with H2O (0.5 L) and brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography, eluent toluene:heptane 2:1->100:0 followed by toluene:EtOAc 95:5 to afford 3-bromo-6-methoxy-pyridin-2-ylamine as a solid (3 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][N:3]=1.[CH3:17][N:18]([CH3:22])[CH2:19][C:20]#[CH:21]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:17][N:18]([CH3:22])[CH2:19][C:20]#[C:21][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][N:3]=1
Reactant: C#CCN(C)C
Reactant: C[Si](C)(C)CCOCOc1ccc(Cl)nc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CN(C)C=O
Product: CN(C)CC#Cc1ccc(OCOCC[Si](C)(C)C)cn1
Temperature: 150 °C

Procedure:
To a mixture of compound 57A (154 mg, 0.593 mmol), N,N-dimethylprop-2-yn-1-amine (0.190 ml, 1.778 mmol), (PPh3)2PdCl2 (62.4 mg, 0.089 mmol), TEA (0.413 ml, 2.96 mmol) in DMF (3 ml) was added copper(I) iodide (11.29 mg, 0.059 mmol). The resulting mixture was heated at 150° C. in a Smith microwave synthesizer for 30 min and purified by flash chromatography to provide the desired compound 57B; LCMS (APCI) m/e 307.
Reaction SMILES: I[C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[N:4][CH:3]=1.C(N(CC)CC)C.[C:26]([Si:28]([CH3:31])([CH3:30])[CH3:29])#[CH:27]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:29][Si:28]([C:26]#[C:27][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[N:4][CH:3]=1)([CH3:31])[CH3:30]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1c1ncc(I)[nH]1
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC[C@H]1c1ncc(C#C[Si](C)(C)C)[nH]1
Yield: 81.8 %

Procedure:
A solution of (S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1 g, 2.75 mmol), triethylamine (1.92 mL, 13.8 mmol) and copper(I) iodide (0.105 g, 0.551 mmol) in DMF (30 mL) was degassed under vacuum and backfilled with nitrogen. Ethynyltrimethylsilane (1.35 g, 13.8 mmol) and Pd(Ph3P)4 (0.159 g, 0.138 mmol) were added and then the reaction was sealed and heated at 50° C. for 1d. The reaction was concentrated to remove the volatiles and the residue was purified on a BIOTAGE® (silica gel, eluted with 0 to 40% ethyl acetate/hexanes) to yield (S)-tert-butyl 2-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (751 mg, 2.25 mmol, 82% yield) as brownish foam.
Reaction SMILES: [C:1]1([S:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.BrCC(OCC)=O.[Cl:21]C1C=CC(S)=CC=1>CC[O-].[Na+]>[Cl:21][C:4]1[CH:5]=[CH:6][C:1]([S:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:2][CH:3]=1
Reactant: CCOC(=O)CSc1ccccc1
Reactant: Sc1ccc(Cl)cc1
Agent: CCOC(=O)CBr
Agent: CC[O-]
Agent: [Na+]
Product: CCOC(=O)CSc1ccc(Cl)cc1

Procedure:
The procedure is as in Example 2 for the preparation of ethyl (phenylthio)acetate starting with ethyl bromoacetate (16.7 g), a 2M ethanolic solution of sodium ethylate (50 cc) and 4-chlorothiophenol (14.5 g). Ethyl (4-chlorophenylthio)acetate (20.7 g) is thereby obtained, and is used in the crude state in the subsequent phases.
Reaction SMILES: [C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([O:25][CH2:26][CH:27]5[CH2:31][CH2:30][CH2:29][N:28]5C(OCC5C=CC=CC=5)=O)=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O>CO.[OH-].[OH-].[Pd+2]>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([O:25][CH2:26][CH:27]5[CH2:31][CH2:30][CH2:29][NH:28]5)=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[C@H](Nc1nccc(-n2cnc3cc(OCC4CCCN4C(=O)OCc4ccccc4)ccc32)n1)c1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: C[C@H](Nc1nccc(-n2cnc3cc(OCC4CCCN4)ccc32)n1)c1ccccc1
Reaction time: 15 h
Yield: 84.2 %

Procedure:
2-[(S)-1-Phenylethylamino]-4-[5-((N-benzyloxycarbonyl-pyrrolidin-2-yl)methoxy)benzimidazol-1-yl]pyrimidine (11 mg) was dissolved in methanol (1.0 mL) and catalytic Pd(OH)2 and trifluoroacetic acid were added and the resulting suspension was stirred under hydrogen atmosphere for 15 hours. Filtration and evaporation of solvent gave N-[(1S)-1-phenylethyl]-4-[5-(2-pyrrolidinylmethoxy)-1H-benzimidazol-1-yl]-2-pyrimidinamine (7.0 mg). Mass spectrum (ESI) 415.5 (M+1).
Reaction SMILES: C([Li])CCC.[CH3:6][Si:7]([CH:10]=[N+:11]=[N-:12])([CH3:9])[CH3:8].[F:13][C:14]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:15]=1[NH:21][C:22]1[CH:29]=[N:28][CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])[C:23]=1[C:24]#[N:25]>C1COCC1.CCOC(C)=O>[F:13][C:14]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:15]=1[NH:21][C:22]1[CH:29]=[N:28][CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])[C:23]=1[C:24]1[N:25]=[N:12][NH:11][C:10]=1[Si:7]([CH3:9])([CH3:8])[CH3:6]
Reactant: N#Cc1c(Nc2ccc(I)cc2F)cncc1-c1ccccc1F
Reactant: C[Si](C)(C)C=[N+]=[N-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[Si](C)(C)c1[nH]nnc1-c1c(Nc2ccc(I)cc2F)cncc1-c1ccccc1F
Reaction time: 0.33 h
Yield: 36.5 %

Procedure:
n-Butyllithium (28 μL, 2.5 M in THF, 0.07 mmol) was added to a solution of (trimethylsilyl)diazomethane (35 μL, 2.0 M in THF, 0.07 mmol) in THF (1 mL) at 0° C., and stirred for 20 minutes. 3-(2-Fluoro-4-iodo-phenylamino)-5-(2-fluoro-phenyl)-isonicotinonitrile (20 mg, 0.05 mmol) was added, and the resulting solution was stirred overnight at room temperature. The reaction solution was diluted with EtOAc and satd. NH4Cl, and filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was purified via Biotage eluting with a gradient of 0 to 75% EtOAc in hexanes to afford the desired product (10 mg, 40%). LC-MS (M+H=548, obsd.=548).
Reaction SMILES: CC1NC(C)=C(C(OCC[Cl:26])=O)C(C2C=CC=C([N+]([O-])=O)C=2)C=1C(OC)=O.[CH3:28][CH:29]([NH:44][CH3:45])[CH2:30][CH:31]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1(C)C=CC=CC=1.C(OCC)C>[ClH:26].[CH3:28][CH:29]([NH:44][CH3:45])[CH2:30][CH:31]([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCl)C1c1cccc([N+](=O)[O-])c1
Agent: CNC(C)CC(c1ccccc1)c1ccccc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: Cl
Reaction time: 25 h

Procedure:
A solution of 3.94 g of methyl 2-chloroethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate and 4.78 g of l,N-dimethyl-3,3-diphenylpropylamine in 12 ml of toluene was refluxed under stirring for 25 hours. Upon completion of the reaction the mixture was diluted with diethyl ether and the l,N-dimethyl-3,3-diphenylpropylamine hydrochloride formed was collected by filtration. The filtrate was then evaporated, and the crude product thus obtained was purified by repeated chromatography on silica gel, using first chloroform, then chloroform: ethyl acetate (85:15 by volume) and lastly ethyl acetate as eluent. The purified product was dissolved in methanol and ethanolic hydrogen chloride was added. The solution was filtered and evaporated to dryness. Repeated washings with warm diethyl ether: acetone (98:2 by volume) afforded 2.98 g of the title compound, m.p. 113°-120° C.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[OH:5][CH2:6][CH2:7][N:8]([CH3:32])[C:9](=[O:31])[C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:18]=2[Cl:27])[CH:13]=[CH:12][C:11]=1[N+:28]([O-:30])=[O:29].C(N(CC)CC)C>C1COCC1>[C:1]([O:5][CH2:6][CH2:7][N:8]([CH3:32])[C:9](=[O:31])[C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:19][C:18]=2[Cl:27])[CH:13]=[CH:12][C:11]=1[N+:28]([O-:30])=[O:29])(=[O:3])[CH3:2]
Reactant: CN(CCO)C(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)OCCN(C)C(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Yield: 44.2 %

Procedure:
Acetyl chloride (2.7 g, 0.0344 mole) was added dropwise in 5 mins. to a solution of N-(2-hydroxyethyl)-N-methyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide (7.2 g, 0.0172 mole), triethylamine (25 ml) and THF (25 ml). The resulting mixture was heated up to and held at reflux for 2.5 hrs., cooled and concentrated. The residue was taken into 500 ml of ether, washed two times with water, dried over MgSO4 and concentrated to 8.6 g of crude product. The crude product was purified on a column of silica gel using ethyl acetate cyclohexane (1:3) as eluent to yield 3.5 g of pure N-[2-(acetoxy)ethyl]-N-methyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide as a gum; nmr (CDCl3) δ 2.04 (s, 3H), 2.92 (s)-3.15 (s) (3H), 3.40 (t)-3.79 (t) (2H); 4.12 (t)-4.40 (t) (2H), 6.80-8.42 (m, 6H); ir (CHCl3) 1750, 1655 Cm-1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[F:15].C(=O)(O)[O-].[Na+].[C:21](Cl)(Cl)=[S:22]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:21]=[S:22])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[F:15]
Reactant: Nc1ccc(Cl)c(-c2ccncc2F)c1
Reactant: S=C(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Product: Fc1cnccc1-c1cc(N=C=S)ccc1Cl
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
The mixture containing 4-chloro-3-(3-fluoropyridin-4-yl)benzenamine (1 eq) and sodium bicarbonate (2 eq) in acetone was treated with thiophosgene (2 eq) and stirred for 5 minutes at 0° C. Reaction then concentrated and partitioned between ethyl acetate and water. Organic layer dried over sodium sulfate and sodium bicarbonate and concentrated to give 4-(2-chloro-5-isothiocyanatophenyl)-3-fluoropyridine. HPLC=5.54 min; MS: MH+=265.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C@@H:10]([NH2:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1)([O-])=O.[H][H]>C1COCC1.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([C@@H:10]([NH2:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1
Reactant: [H][H]
Reactant: C[C@H](N)c1cccc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: C1CCOC1
Product: C[C@H](N)c1cccc(N)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 38.5 %

Procedure:
(S)-1-(3-nitrophenyl)-1-aminoethane (approx. 80% pure, 75.2 mg) was dissolved in THF (2 mL) and 10% Pd/C (13.8 mg) was added. The system was fitted with a balloon of hydrogen and purged 3×, the mixture left stirring 16 h at room temperature. Filtered the solution through Celite®, washing thoroughly with methanol, and the solvent removed in vacuo. The residue was eluted on silica gel (3-6%(2M NH3 in MeOH)/CH2Cl2) to yield 23.7 mg of the title compound. 1H NMR (500 MHz, CDCl3): δ 7.13 (t, J=7.7 Hz, 1H); 6.74 (m, 1H); 6.71 (m, 1H); 6.58 (m, 1H); 4.03 (q, J=6.7 Hz, 1H); 3.68 (br s, 2H); 1.37 (d, J=6.7 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[C:11]([C@@H:12]([OH:15])[CH2:13][OH:14])=[C:10]([CH3:16])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([Sn](=O)CCCC)CCC.[S:27](Cl)([C:30]1[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=1)(=[O:29])=[O:28].CCN(CC)CC>C(Cl)Cl>[CH3:34][C:33]1[CH:35]=[CH:36][C:30]([S:27]([O:14][CH2:13][C@@H:12]([C:11]2[C:2]([Br:1])=[C:3]3[C:8](=[CH:9][C:10]=2[CH3:16])[N:7]=[CH:6][CH:5]=[CH:4]3)[OH:15])(=[O:29])=[O:28])=[CH:31][CH:32]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Cc1cc2ncccc2c(Br)c1[C@@H](O)CO
Agent: CCCC[Sn](=O)CCCC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(S(=O)(=O)OC[C@H](O)c2c(C)cc3ncccc3c2Br)cc1
Temperature: 25 °C

Procedure:
To a stirred solution of (R)-1-(5-bromo-7-methylquinolin-6-yl)ethane-1,2-diol (197 mg, 0.70 mmol) in CH2Cl2 (97 mL), dibutyltinoxide (3.3 mg, 0.01 mmol), TsCl (150 mg, 0.79 mmol), and Et3N (0.12 mL, 0.83 mmol) were added at 0° C. The reaction mixture was allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous NH4Cl, and then diluted with CH2Cl2. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 5 to 100% ethyl acetate/hexanes) to give (R)-2-(5-bromo-7-methylquinolin-6-yl)-2-hydroxyethyl 4-methylbenzenesulfonate. LCMS-ESI+ (m/z): [M+H]+ calc'd for C19H19BrNO4S: 436.02; Found: 436.1.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH2:22][CH2:21]1.CCOC(C)=O>CN(C=O)C>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:30][C:29]2[CH:28]=[CH:27][C:26]([N:23]3[CH2:24][CH2:25][O:20][CH2:21][CH2:22]3)=[CH:32][CH:31]=2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]
Reactant: Nc1ccc(N2CCOCC2)cc1
Reactant: CC(C)(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)N1C(=O)C(Nc2ccc(N3CCOCC3)cc2)=C(c2ccccc2)S1(=O)=O
Yield: 55.9 %

Procedure:
A solution of 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.400 g, 1.33 mmol) and 4-morpholinoaniline (0.476 g, 2.67 mmol) in DMF (4 mL) was heated at 140° C. for 15 mins in a microwave reactor. EtOAc was then added, and the resulting mixture was washed with brine and evaporated. The residue was purified by silica gel column chromatography using a 1:1 mixture of petroleum ether and EtOAc as eluant, to give the title compound (0.328 g, 56%) as a solid; 1H NMR (500 MHz, CDCl3): δ 7.23-7.18 (m, 1H), 7.15-7.09 (m, 4H), 6.62 (d, 2H), 6.52 (d, 2H), 3.83 (t, 4H), 3.00 (t, 4H), 1.79 (s, 9H); Mass Spectrum: M−H+ 440.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][NH2:5].[CH2:6]([N:10]=[C:11]=[O:12])[CH2:7][CH2:8][CH3:9]>O1CCCC1>[CH2:6]([NH:10][C:11]([N:4]([CH2:3][CH2:2][OH:1])[NH2:5])=[O:12])[CH2:7][CH2:8][CH3:9]
Reactant: NNCCO
Reactant: CCCCN=C=O
Solvent: C1CCOC1
Product: CCCCNC(=O)N(N)CCO
Temperature: 25 °C

Procedure:
To 7.61 g (0.1 moles) 2-hydroxyethylhydrazine in 150 mL tetrahydrofuran was added dropwise over a period of about 1/2 hour with stirring 9.91 g (0.1 mole) butylisocyanate in 50 mL tetrahydro-furan. At the end of the addition period stirring was continued until the solution cooled to room temperature. A small amount of precipitate was removed by filtration, and the solvent was evaporated to yield a viscous pale oil, N-butyl-1-(2-hydroxyethyl)hydrazinecarboxamide quantitatively. This structure was confirmed by NMR analysis.
Reaction SMILES: [CH2:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].C(N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>C(Cl)Cl>[CH2:1]([N:4]1[CH2:5][CH2:6][CH:7]([C:10]2[CH:11]=[C:12]([O:16][S:25]([CH3:24])(=[O:27])=[O:26])[CH:13]=[CH:14][CH:15]=2)[CH2:8][CH2:9]1)[CH2:2][CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CCCN1CCC(c2cccc(O)c2)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCN1CCC(c2cccc(OS(C)(=O)=O)c2)CC1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A solution of 3-(1-propyl-piperidin-4-yl)-phenol (340 mg) and triethylamine (187 mg) in 20 ml of CH2Cl2 was cooled to 0° C. Then methanesulfonyl chloride (194 mg) dissolved in 10 ml of CH2Cl2 was added dropwise. The reaction mixture was allowed to reach room temperature and then stirred for 2.5 h at 25° C. The reaction was finally quenched with water. The organic layer was separated and washed with 10% HCl and then 10% Na2CO3.
Reaction SMILES: C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O.[CH2:22]([O:29][C@@H:30]1[C@@H:35]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:34]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:33]([CH2:52][O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:32][C@H:31]1[O:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][OH:78])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(Cl)Cl.S(=O)(=O)(O)O>C(O)C>[CH2:22]([O:29][C@@H:30]1[C@@H:35]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:34]([O:44][CH2:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[C@@H:33]([CH2:52][O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:32][C@H:31]1[O:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH:77]=[O:78])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: OCCCCCCCCCCCCCCCCO[C@@H]1O[C@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCO
Product: O=CCCCCCCCCCCCCCCCO[C@@H]1O[C@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 76 %

Procedure:
PDC oxidation of 16-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyloxy)-n-hexadecanol. Under an atmosphere of nitrogen, pyridinium dichromate (320 mg, 0.851 mmol) was added to a dry methylene chloride solution (6 mL) of 16-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyloxy)-n-hexadecanol (455 mg, 0.583 mmol). The resulting brown slurry was stirred at room temperature under nitrogen. TLC analysis (visualization by UV and char with 10% sulfuric acid in ethanol) of the reaction mixture indicated complete consumption of the starting material and the formation of a new compound after 17 h. The reaction mixture was treated with ether (10 mL), filtered through silica gel and Celite with an ether wash (25 mL) and concentrated to an off-white oil. Chromatographic purification (silica gel, 10% ethyl acetate in hexanes) afforded 345 mg (0.443 mmol, 76%) of 16-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyloxy)-n-hexadecanal as a clear oil. Rf =0.72 (silica gel, 30% ethyl acetate in hexanes); 1H NMR (CDCl3, 300 MHz) δ: 9.75 (t, J=1.5 Hz, 1H), 7.30 (m, 20H), 4.95 (d, J=11.7 Hz, 2H), 4.75 (m, 2H), 4.63 (d, J=11.7 Hz, 1H), 4.43 (d, J=4.5 Hz, 2H), 4.36 (d, J=7.8 Hz, 1H), 3.65 (m, 2H), 3.82 (dt, J=8.7, 1.5 Hz, 1H), 3.56 (m, 6H), 2.40 (dt, J=7.5, 1.5 Hz, 2H), 1.60 (m, 4H), 1.26 (m, 24 H); MS (FAB+): 801.3 (M+Na, 14), 785.3 ((M+Li)+, 29), 253.1 (10), 181.1 (100), 160.0 (16), 136.0 (21), 123.0 (12).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6](Cl)=[O:7])([O-:3])=[O:2].[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][N:15]=1.N1C=CC=CC=1>C(Cl)Cl>[Br:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:6]([C:5]2[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=2[N+:1]([O-:3])=[O:2])=[O:7])=[N:15][CH:16]=1
Reactant: Nc1ccc(Br)cn1
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1ccc(Br)cn1)c1ccccc1[N+](=O)[O-]
Yield: 77.9 %

Procedure:
A solution of 2-nitrobenzoyl chloride (3.70 g, 20 mmol, 1.0 equiv), 2-amino-5-bromopyridine (3.50 g, 1.0 equiv), pyridine (10 mL) in 25 mL of methylene chloride was stirred overnight. The volatile was evaporated, flash chromatography on silica gel gave N-(5-bromo-2-pyridinyl)-(2-nitro)phenylcarboxamide (5.02 g, 77%). MS found for C12H9BrN3O3 (M+H)+: 322.