Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([Si:24]([C:37]2[CH:42]=[CH:41][C:40]([Br:43])=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.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>[Br:43][C:40]1[CH:39]=[CH:38][C:37]([Si:24]([C:31]2[CH:32]=[CH:33][C:34]([C:4]3[C:5]4[S:6][C:7]5[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=5[C:9]=4[CH:1]=[CH:2][CH:3]=3)=[CH:35][CH:36]=2)([C:21]2[CH:22]=[CH:23][CH:18]=[CH:19][CH:20]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:42][CH:41]=1
Reactant: OB(O)c1cccc2c1sc1ccccc12
Reactant: Brc1ccc([Si](c2ccccc2)(c2ccccc2)c2ccc(Br)cc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Product: Brc1ccc([Si](c2ccccc2)(c2ccccc2)c2ccc(-c3cccc4c3sc3ccccc34)cc2)cc1
Temperature: 25 °C
Yield: 79.4 %

Procedure:
A mixture solution of dibenzo[b,d]thiophen-4-ylboronic acid (2.5 g, 10.96 mmol), bis(4-bromophenyl)diphenylsilane (11.92 g, 24.11 mmol), Pd(PPh3)4 (0.253 g, 0.219 mmol), and K2CO3 (9.09 g, 65.8 mmol) in toluene (90 mL) and water (30 mL) was stirred at 90° C. under nitrogen overnight. After cooling to room temperature, the organic phase was isolated, and the aqueous phase was extracted with toluene. The combined organic solution was dried over Na2SO4. Upon evaporation of the solvent, the residue was purified by column chromatography on silica gel with hexane:DCM(9/1, v/v) as eluent to yield (4-bromophenyl)(4-(dibenzo[b,d]thiophen-4-yl)phenyl)diphenylsilane (5.2 g, 79%) as a white powder.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[N:13]=[N:14][NH:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]#[N:27])#[N:2].[CH2:28]([N:31]=[C:32]=[O:33])[CH2:29][CH3:30]>CCOCC>[CH2:28]([NH:31][C:32]([N:13]([C:4]1[CH:5]=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:7]=[CH:8][C:3]=1[C:1]#[N:2])[N:14]=[N:15][C:16]1[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][C:17]=1[C:26]#[N:27])=[O:33])[CH2:29][CH3:30]
Reactant: CCCN=C=O
Reactant: N#Cc1ccc(C(F)(F)F)cc1N=NNc1cc(C(F)(F)F)ccc1C#N
Solvent: CCOCC
Product: CCCNC(=O)N(N=Nc1cc(C(F)(F)F)ccc1C#N)c1cc(C(F)(F)F)ccc1C#N
Reaction time: 24 h

Procedure:
To a solution of 5.4 g. (0.014 mol.) of 1,3-bis(2cyano-5-trifluoromethylphenyl)triazene in 500 ml. of ether is added 15 ml. of propyl isocyanate. The reaction mixture is stirred at 25° for 24 hours after which time the precipitated product is collected by filtration and washed with ether to give 3-(N-propylcarbamoyl)-1,3-bis(2-cyano-5-trifluoromethylphenyl)triazene, m.p. 138°-140° (dec.).
Reaction SMILES: [C:1]1([S:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH:21]=3)[NH:16][N:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:30](O[BH-](OC(=O)C)OC(=O)C)(=O)C.C=O.O.[OH-].[Na+]>C(#N)C.C(Cl)(Cl)Cl>[CH3:30][N:27]1[CH2:28][CH2:29][CH:24]([O:23][C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[S:11]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)(=[O:12])=[O:13])[CH2:25][CH2:26]1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: O=S(=O)(c1cccc2ccccc12)c1n[nH]c2ccc(OC3CCNCC3)cc12
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CC#N
Product: CN1CCC(Oc2ccc3[nH]nc(S(=O)(=O)c4cccc5ccccc45)c3c2)CC1
Reaction time: 2.5 h
Yield: 101.4 %

Procedure:
A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (57.7 mg, 0.142 mmol) in acetonitrile was treated in three portions with odium triacetoxyborohydride (54 mg, 0.26 mmol) and 37% formaldehyde in water (0.1 mL, 1.3 mmol), stirred at ambient temperatures for 2.5 hours and poured into excess chloroform and 1.0 N sodium hydroxide. The phases were separated. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography with 0.5% ammonium hydroxide/5.0% methanol in chloroform to give 5-(1-methylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole (47.9 mg, 0.144 mmol) as a light orange foam. The foam was dispersed in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 82° C. in for 10 hours to yield the title product as a light orange solid, mp 252-4° C.; Mass spectrum (+EI, [M+H]+) m/z 422. 1HNMR (300 MHz, DMSO-d6): δ14.16 (s, 1H), 10.06-10.17 (m*, 1H), 8.73-8.75 (m, 1H), 8.54-8.56 (m, 1H), 8.26-8.28 (m, 1H), 8.02-8.05 (m, 1H), 7.72 (t, 1H, J=7.81 Hz), 7.55-7.63 (m, 3H), 7.29-7.37 (m*, 1H), 7.10-7.20 (m*, 1H), 4.58-4.77 (m*, 1H), 3.45-3.50 (m, 1H), 3.07-3.20 (m, 2H), 2.75 (s, 3H), 1.70-2.20 ppm (m*, 4H). *Conformational isomers due to protonation of tertiary amine.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1.C(OCC)(=O)C.O.[CH3:22][N:23](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[O:4]([C:5]1[N:6]=[C:7]([C:22]#[N:23])[CH:8]=[CH:9][CH:10]=1)[C:3]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:2]=1
Reactant: CN(C)C=O
Reactant: Brc1ccccc1Oc1ccccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Solvent: O
Product: N#Cc1cccc(Oc2ccccc2)n1
Temperature: 100 °C
Reaction time: 1 h
Yield: 67 %

Procedure:
Next, to a solution of the resulting 2-bromo-phenoxy-pyridine (1.0 g, 4.0 mmol) in N,N-dimethylformamide (30 mL) were added zinc cyanide (940 mg, 8.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (924 mg, 0.8 mmol) under nitrogen atmosphere, and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was allowed to room temperature, ethyl acetate and water were added for partitioning, the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), and 6-phenoxy-pyridine-2-carbonitrile (524 mg, 67%) was obtained as a white solid.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:23]=[C:24]([CH3:26])[CH:25]=3)[O:18][CH2:19][CH2:20][CH2:21][OH:22])(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(N(CC)C(C)C)(C)C.CS(C)=O>ClCCl>[CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:23]=[C:24]([CH3:26])[CH:25]=3)[O:18][CH2:19][CH2:20][CH:21]=[O:22])(=[O:12])=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: Cc1cc(OCCCO)cc(OS(=O)(=O)c2cccc3cnccc23)c1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(OCCC=O)cc(OS(=O)(=O)c2cccc3cnccc23)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.7 %

Procedure:
Sulfur trioxide pyridine complex (240 mg, 1.5 mmol) was added to a solution of 3-[3-(5-isoquinolinylsulfonyloxy)-5-methylphenoxy]propanol (190 mg, 0.5 mmol), as prepared in the preceding step, N,N-diisopropylethylamine (0.2 mL, 1.6 mmol) and anhydrous dimethyl sulfoxide (0.1 mL, 1.4 mmol) in anhydrous dichloromethane (20 mL). The reaction mixture was stirred at ambient temperature for 1 hour and then quenched with 10% aqueous citric acid (30 mL). The mixture was extracted into dichloromethane (3×30 mL), and the dichloromethane solution was washed with 10% aqueous citric acid (30 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography (3:1 ethyl acetate/dichloromethane) to give the title compound as a colorless oil (135 mg, 72%). 1H-NMR (300 MHz, CDCl3) δ 9.79 (s, 1H), 9.46 (s, 1H), 8.80 (d, J=6.2 Hz, 1H), 8.59 (d, J=5.8 Hz, 1H), 8.37 (d, J=7.5 Hz, 1H), 8.34 (d, J=8.3 Hz, 1H), 7.71 (t, J=7.7 Hz, 1H), 6.56 (s, 1H), 6.32 (s, 1H), 6.24 (s, 1H), 4.09 (t, J=6.0 Hz, 2H), 2.81 (t, J=6.0 Hz, 2H), 2.17 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[C:11]([Cl:17])[CH:10]=1)([CH3:7])[CH3:6])[CH3:2].ClC1C=C(O)C=CC=1C=O.C(CC(Br)(C)C([O-])=O)C.[CH3:38][O:39][CH2:40][CH2:41][C:42]1[C:47]([C:48](O)=[O:49])=[CH:46][N:45]=[C:44]([C:51]2[CH:56]=[CH:55][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:53][CH:52]=2)[N:43]=1.COC(=O)CC(=O)CCOC>>[CH2:1]([O:3][C:4](=[O:18])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:48]([C:47]2[C:42]([CH2:41][CH2:40][O:39][CH3:38])=[N:43][C:44]([C:51]3[CH:52]=[CH:53][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:55][CH:56]=3)=[N:45][CH:46]=2)=[O:49])=[C:11]([Cl:17])[CH:10]=1)([CH3:7])[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CN)c(Cl)c1
Reactant: COCCc1nc(-c2ccc(C(F)(F)F)cc2)ncc1C(=O)O
Agent: CCCC(C)(Br)C(=O)[O-]
Agent: COCCC(=O)CC(=O)OC
Agent: O=Cc1ccc(O)cc1Cl
Product: CCOC(=O)C(C)(C)Oc1ccc(CNC(=O)c2cnc(-c3ccc(C(F)(F)F)cc3)nc2CCOC)c(Cl)c1

Procedure:
In analogy to the procedures described in example 26B] and 26C], 2-(4-aminomethyl-3-chloro-phenoxy)-2-methyl-propionic acid ethyl ester (prepared from 2-chloro-4-hydroxy-benzaldehyde by reaction with ethyl-bromoisobutyrate as described in example 52A] followed by oxim formation and reduction as described in examples 97A] and 97B]) was reacted with 4-(2-methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carboxylic acid (prepared from 5-methoxy-3-oxo-pentanoic acid methyl ester, in analogy to the procedures described in examples 27C] and 27D] followed by saponification in analogy to the procedure described in example 53B]) to give 2-[3-chloro-4-({[4-(2-methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-phenoxy]-2-methyl-propionic acid ethyl ester, which was subsequently saponified to yield the title compound as light yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=[C:11](Cl)[N:10]=1.[NH2:19][CH2:20][CH2:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25]([NH2:32])[N:24]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[NH2:32][C:25]1[N:24]=[C:23]([NH:22][CH2:21][CH2:20][NH:19][C:11]2[CH:12]=[CH:13][C:14]([N+:15]([O-:17])=[O:16])=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:10]=2)[CH:28]=[CH:27][C:26]=1[N+:29]([O-:31])=[O:30]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1-c1ccc(Cl)cc1Cl
Reactant: NCCNc1ccc([N+](=O)[O-])c(N)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Nc1nc(NCCNc2ccc([N+](=O)[O-])c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]

Procedure:
1 mmol of 2-(2,4-dichlorophenyl)-6-chloro-3-nitropyridine was taken with 2 mmol of (2-aminoethyl)(6-amino-5-nitro(2-pyridyl))amine and 3 mmol of N,N-diisopropylethylamine in 2 ml of DMF at 80° C. for two hours. The reaction mixture was concentrated in vacuo and diluted with water and ethyl acetate. The solution was extracted three times with ethyl acetate, dried over sodium sulfate, and purified by column chromatography eluting with 5-10% methanol/methylene chloride.
Reaction SMILES: [C:1]([NH:9][CH:10]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:11]([OH:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([O:26][CH:27](OCC)OCC)[CH3:25].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C1C=CC=CC=1>[CH2:15]([O:14][C:12]([C@H:11]1[O:17][CH:27]([O:26][CH2:24][CH3:25])[N:9]([C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@H:10]1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:13])[CH3:16]
Reactant: CCOC(OCC)OCC
Reactant: CCOC(=O)C(O)C(NC(=O)c1ccccc1)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: c1ccccc1
Product: CCOC(=O)[C@H]1OC(OCC)N(C(=O)c2ccccc2)[C@H]1c1ccccc1

Procedure:
[R-(R*,S*)]-β-(Benzoylamino)-α-hydroxybenzenepropanoic acid, ethyl ester (1.16 mmol) is suspended in benzene (10 ml), and triethoxymethane (3.44 mmol) and PPTS (72 mg) are added. Heating to reflux provides the title compound.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=[O:7].[CH:12](O)([CH3:14])[CH3:13]>>[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([O:8][CH:12]([CH3:14])[CH3:13])=[O:7]
Reactant: O=C(O)c1cccc(CCl)c1
Reactant: CC(C)O
Product: CC(C)OC(=O)c1cccc(CCl)c1

Procedure:
Isopropyl 3-(chloromethyl)benzoate 13b was prepared by reacting 3-(chloromethyl)benzoic acid 23 with isopropanol according to the procedure described for the compound 13a in Example 17 (scheme 7). The benzoate 13b was isolated as colorless oil in 87% yield (1.85 g). 1H NMR (400 MHz, CDCl3): δ 1.37 (6H, m); 4.62 (2H, s); 5.27 (2H, m); 7.43 (1H, m); 7.57 (1H, broad d); 7.98 (1H, broad d); 8.04 (1H, s).
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][OH:72])[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][CH:71]=[O:72])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: OCCCCCCCCCCO[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: CCO
Solvent: ClCCl
Product: O=CCCCCCCCCCO[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 770 %

Procedure:
PDC oxidation of 10-(2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyloxy)-n-decanol. Under an atmosphere of nitrogen, pyridinium dichromate (400 mg, 1.036 mmol) was added to a dry methylene chloride solution (10 mL) of 10-(2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyloxy)-n-decanol (450 mg, 0.646 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 15 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, 20% ethyl acetate in hexanes) afforded 345 mg (0.497 mmol, 770%) of 10-(2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyloxy)-n-decanal as a clear oil. Rf =0.50 (silica gel, 300 ethyl acetate in hexanes); 1H NMR (CDCl3, 300 MHz) δ: 9.76 (dt, J=5.1, 1.5 Hz, 1H), 7.31 (m, 20H), 4.93 (d, J=6.6 Hz, 1H), 4.91 (d, J=2.4 Hz, 1H), 4.78 (d, J=2.1 Hz, 1H), 4.72 (d, J=12.0 Hz, 1H), 4.67 (m, 2H), 4.57 (dd, J=12.0, 10.8 Hz, 2H), 4.09 (t, J=6.9 Hz, 1H), 4.03 (d, J=9.3 Hz, 1H), 3.96 (dd, J=12.0, 2.7 Hz, 1H), 3.82 (m, 3H), 3.68 (m, 1H), 3.40 (dt, J=9.6, 6.6, Hz, 2H), 2.41 (dt, J=7.2, 1.8 Hz, 2H), 1.64 (m, 4H), 1.32 (m, 12H); MS (FAB+): 717.1 ((M+Na)+, 33), 701.1 ((M+Li)+, 100), 671.1 (8), 615.1 (7), 455.1 (12), 439.1 (10), 423.1 (20), 243.1 (10), 181.1 (17), 160.0 (20).
Reaction SMILES: Br[C:2]1[C:3]([CH3:28])=[C:4]([N:8]([CH2:13][C:14]2[CH:26]=[CH:25][C:17]([O:18][CH2:19][C:20]([O:22]CC)=[O:21])=[C:16]([CH3:27])[CH:15]=2)[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:6][CH:7]=1.[C:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)#[N:30]>>[CH2:9]([N:8]([CH2:13][C:14]1[CH:26]=[CH:25][C:17]([O:18][CH2:19][C:20]([OH:22])=[O:21])=[C:16]([CH3:27])[CH:15]=1)[C:4]1[C:3]([CH3:28])=[C:2]([C:34]2[CH:35]=[CH:36][C:31]([C:29]#[N:30])=[CH:32][CH:33]=2)[CH:7]=[CH:6][CH:5]=1)[CH2:10][CH2:11][CH3:12]
Reactant: CCCCN(Cc1ccc(OCC(=O)OCC)c(C)c1)c1cccc(Br)c1C
Reactant: N#Cc1ccc(B(O)O)cc1
Product: CCCCN(Cc1ccc(OCC(=O)O)c(C)c1)c1cccc(-c2ccc(C#N)cc2)c1C

Procedure:
Prepared from ethyl (4-{[(3-bromo-2-methylphenyl)(butyl)amino]methyl}-2-methylphenoxy)acetate and 4-cyanophenylboronic acid using the procedure described for Example 25 (Method A).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:29](=[O:30])[N:28]([CH3:31])[C:12]2[N:13]([CH3:27])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20](=O)[CH:21]=[CH:22]N(C)C)=[CH:16][CH:15]=3.[OH:32][CH2:33][CH2:34][NH:35][NH2:36]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:29](=[O:30])[N:28]([CH3:31])[C:12]2[N:13]([CH3:27])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20]1[N:35]([CH2:34][CH2:33][OH:32])[N:36]=[CH:22][CH:21]=1)=[CH:16][CH:15]=3
Reactant: NNCCO
Reactant: CN(C)C=CC(=O)c1ccc2c(c1)c1cc(-c3ccc(Cl)cc3Cl)c(=O)n(C)c1n2C
Product: Cn1c(=O)c(-c2ccc(Cl)cc2Cl)cc2c3cc(-c4ccnn4CCO)ccc3n(C)c21

Procedure:
The process is carried out as in Example 37 above, with the compound from preparation 1.10, 3-(2,4-dichlorophenyl)-6-[3-(dimethylamino)prop-2-enoyl]-1,9-dimethyl-1,9-dihydro-2H-pyrido[2,3-b]indol-2-one and 2-hydroxyethylhydrazine
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13]O)[CH:5]=[N:6][CH:7]=1.S(Cl)([Cl:17])=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][Cl:17])[CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: OC[C@@H]1CCCN1c1cncc(Br)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: ClC[C@@H]1CCCN1c1cncc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 85.7 %

Procedure:
To a solution of (S)-(1-(5-bromopyridin-3-yl)pyrrolidin-2-yl)methanol (0.060 g, 0.233 mmol) in DCM (1 mL) cooled to 0° C. was added thionyl chloride (0.112 g, 0.932 mmol) dropwise. The reaction mixture was stirred at this temperature for 30 min and then allowed to warm up to room temperature and stirring was continued over night. The mixture was diluted with DCM, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with DCM (2×20 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound (0.055 g, 86%) as an orange oil. MS: 275.0, 277.0 (M+H+).
Reaction SMILES: [BrH:1].C(O)(=O)C.C(OC([NH:16][CH:17]1[CH2:19][CH:18]1[C:20]1[C:21]([F:38])=[CH:22][C:23]2[C:33](=[O:34])[C:32]([C:35]([OH:37])=[O:36])=[CH:31][N:25]3[C@@H:26]([CH3:30])[CH2:27][O:28][C:29]=1[C:24]=23)=O)C1C=CC=CC=1.C(Cl)(Cl)Cl>O>[BrH:1].[NH2:16][CH:17]1[CH2:19][CH:18]1[C:20]1[C:21]([F:38])=[CH:22][C:23]2[C:33](=[O:34])[C:32]([C:35]([OH:37])=[O:36])=[CH:31][N:25]3[C@@H:26]([CH3:30])[CH2:27][O:28][C:29]=1[C:24]=23
Reactant: C[C@H]1COc2c(C3CC3NC(=O)OCc3ccccc3)c(F)cc3c(=O)c(C(=O)O)cn1c23
Agent: Br
Solvent: O
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: C[C@H]1COc2c(C3CC3N)c(F)cc3c(=O)c(C(=O)O)cn1c23
Reaction time: 1 h
Yield: 68.2 %

Procedure:
To 0.5 ml of a 30% hydrogen bromide-acetic acid solution was added with ice-cooling, 50 mg of (S)-10-(2-benzyloxycarbonylaminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid. The resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. To the residue obtained were added 5 ml of chloroform and 5 ml of water in this order. The aqueous layer was separated. The solvent was removed by distillation under reduced pressure. Diethyl ether was added to the residue obtained and the resulting crystals were collected by filtration to obtain 30 mg (yield: 68.2%) of (S)-10-(2-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid hydrobromide.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:19]([N:20]2[CH2:24][CH2:23][CH2:22][C@@H:21]2[CH3:25])=[N:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:26]([O:28]C)=[O:27])[CH:16]=2)[N:11]=1.[OH-].[Na+].O>O1CCCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:19]([N:20]2[CH2:24][CH2:23][CH2:22][C@@H:21]2[CH3:25])=[N:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:26]([OH:28])=[O:27])[CH:16]=2)[N:11]=1
Reactant: COC(=O)c1ccc2nc(-c3nc4ccccc4s3)c(N3CCC[C@@H]3C)nc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: C[C@H]1CCCN1c1nc2cc(C(=O)O)ccc2nc1-c1nc2ccccc2s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.1 %

Procedure:
To a solution of methyl 2-(1,3-benzothiazol-2-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylate (80 mg, 0.20 mmol) in tetrahydrofuran (20 mL) was added NaOH (23.8 mg, 0.60 mmol) and water (1 mL). The resulting solution was stirred overnight at room temperature and then concentrated in vacuo, adjusted the pH to 7 with HCl (3 N). The product was collected and filtered to afford 2-(1,3-benzothiazol-2-yl)-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylic acid as a light yellow solid (43.8 mg, 57%).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[C:11]([C:13]1([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH:24]=2)[CH2:18][CH2:17][C:16]2([O:22][CH2:21][CH2:20][O:19]2)[CH2:15][CH2:14]1)#N.S(=O)(O)[O-:38].[Na+]>C1(C)C=CC=CC=1>[CH:32]1([O:31][C:25]2[CH:24]=[C:23]([C:13]3([CH:11]=[O:38])[CH2:18][CH2:17][C:16]4([O:19][CH2:20][CH2:21][O:22]4)[CH2:15][CH2:14]3)[CH:28]=[CH:27][C:26]=2[O:29][CH3:30])[CH2:36][CH2:35][CH2:34][CH2:33]1
Reactant: COc1ccc(C2(C#N)CCC3(CC2)OCCO3)cc1OC1CCCC1
Reactant: O=S([O-])O
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc(C2(C=O)CCC3(CC2)OCCO3)cc1OC1CCCC1
Reaction time: 18 h

Procedure:
Diisobutylaluminum hydride (1.0M in toluene, 8.13 mL, 8.13 mmol) was added dropwise to a solution of 4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)cyclohexane (1.16 g, 3.19 mmol) dissolved in toluene (20 mL) under an argon atmosphere. After 18 h at room temperature, saturated aqueous sodium bisulfite (100 mL) was added and the mixture was extracted three times with dichloromethane. The combined organic extract was washed with brine, was dried (potassium carbonate) and was evaporated. Purification by flash chromatography, eluting with 4:1 hexanes/ethyl acetate, provided a clear colorless oil. 1H NMR(400 MHz, CDCl3) δ 9.35 (s, 1H), 6.88 (br s, 2H), 6.80 (s, 1H), 4.73 (m, 1H), 3.95 (m, 4H), 3.85 (s, 3H), 2.33 (m, 2H), 2.10 (m, 2H), 1.57-1.99 (m, 12H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([N+:16]([O-])=O)[CH:3]=1.[S:19]1[CH:23]=[CH:22][CH:21]=[C:20]1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C>[NH2:16][C:4]1[CH:3]=[C:2]([C:20]2[S:19][CH:23]=[CH:22][CH:21]=2)[CH:7]=[CH:6][C:5]=1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]
Reactant: OB(O)c1cccs1
Reactant: CC(C)(C)OC(=O)Nc1ccc(Br)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1N

Procedure:
A mixture of tert-butyl (4-bromo-2-nitrophenyl)carbamate (19.4 g, 61.2 mmol), thiophene-2-boronic acid (9.94 g, 77.7 mmol) and K2CO3 (22.2 g, 160 mmol) in 60 mL of dioxane and 60 mL of water was degassed by bubbling nitrogen through the mixture for 30 min. Next, Pd[PPh3]4 (5.25 g, 4.53 mmol) was added and the heterogeneous mixture was warmed to reflux for 20 h. The mixture was cooled and diluted with ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated. The resulting solid was dissolved in diethylether (500 mL) and filtered through a pad of silica. The solvents were removed under reduced pressure to yield the yellow-brown solid: 1H NMR (600 MHz, CDCl3): δ 9.65 (s, 9 H), 8.58 (d, J=8.8 Hz, 1 H), 8.39 (d, J=2.1 Hz, 1 H), 7.81 (dd, J=8.8, 1.8 Hz, 1 H), 7.32 (m, 2 H), 7.09 (dd, J=5.3, 3.8 Hz, 1 H), 1.54 (s, 9 H); MS (ESI+): cal'd [M+Na]+ 343.1, obs'd 343.1.