Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:19]3[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22]4[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=4[N:20]=3)=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]1[C:43]([O:44][CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])=[CH:42][C:41]([CH2:53][OH:54])=[C:40]([Sn](C)(C)C)[CH:39]=1>O1CCOCC1.CCOC(C)=O>[CH3:36][O:37][C:38]1[C:43]([O:44][CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])=[CH:42][C:41]([CH2:53][OH:54])=[C:40]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]([C:19]4[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:22]5[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=5[N:20]=4)=[N:7][N:8]3[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)[CH:39]=1
Reactant: COc1cc([Sn](C)(C)C)c(CO)cc1OCOCC[Si](C)(C)C
Reactant: C[Si](C)(C)CCOCn1nc(-c2nc3ccccc3n2COCC[Si](C)(C)C)c2ccc(I)cc21
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COc1cc(-c2ccc3c(-c4nc5ccccc5n4COCC[Si](C)(C)C)nn(COCC[Si](C)(C)C)c3c2)c(CO)cc1OCOCC[Si](C)(C)C
Yield: 60 %

Procedure:
6-Iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazol-2-yl}-1H-indazole [Example 24(a), step (v)] (300 mg, 0.48 mmol) and [4-methoxy-5-(2-trimethylsilanyl-ethoxymethoxy)-2-trimethylstannanyl-phenyl]-methanol (282 mg, 0.63 mmol) were stirred in dioxane (8 mL) under argon at 98° C. for 16 h. The reaction was allowed to cool and was diluted with EtOAc. Organics were washed with sat NaHCO3 and brine, dried (Na2SO4), and concentrated in vacuo. Purification by silica gel chromatography (20% EtOAc/hexanes) gave 224 mg (60%) of 6-[5-methoxy-2-hydroxymethyl-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-indazol as a faint yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.70 (d, 1H, J=8.4 Hz), 7.89–7.92 (m, 1H), 7.63–7.66 (m, 2H), 7.34–7.41 (m, 4H), 6.91 (s, 1H), 6.29 (s, 2H), 5.83 (s, 2H), 5.36 (s, 2H), 4.55 (s, 2H), 3.78–3.92 (m, 5H), 3.59–3.70 (m, 4H), 0.83–1.04 (m, 6H), 0.03 (s, 9H), −0.04 (s, 9H), −0.13 (s, 9 Hz).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][N:9]=[C:10]=[S:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[NH2:12][C:13]1[S:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[N:17]=1.C(OCC)(=O)C>CN(C)C=O>[C:1]1([CH2:7][CH2:8][NH:9][C:10]([NH:12][C:13]2[S:14][C:15]3[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=3[N:17]=2)=[S:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: S=C=NCCC1=CCCCC1
Reactant: Nc1nc2ccccc2s1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: S=C(NCCC1=CCCCC1)Nc1nc2ccccc2s1
Temperature: 25 °C
Yield: 40.5 %

Procedure:
A solution of 2-(1-cyclohexenyl)ethyl isothiocyanate (3.3 g, 20 mmol) and 2-aminobenzothiazole (3.0 g, 20 mmol) in N,N-dimethylformamide (50 mL) was heated at 100° C. for 17.5 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, 1N aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.57 g (40%) of the title product:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].Br[C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1>>[CH3:34][O:33][C:30]1[N:31]=[CH:32][C:27]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]3[C:11]([C:12]([F:14])([F:13])[F:15])=[CH:10][C:9]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[N:8][C:7]=23)=[CH:28][CH:29]=1
Reactant: COc1ccc(Br)cn1
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: COc1ccc(C#Cc2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)cn1

Procedure:
The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (355 mg, 1.0 mmol) and commercially available 5-bromo-2-methoxypyridine (169 mg, 1.0 mmol) according to general procedure II. Obtained as a red solid (85 mg, 18%). MS (ISP) 463.2 [(M+H)+]; mp 166-168° C.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:14]([C:16]3[CH:17]=[C:18]([Cl:30])[C:19]([C:28]#[N:29])=[C:20]4[C:26]=3[O:25][CH:24]([CH3:27])[CH2:23][NH:22][CH2:21]4)[CH3:15])[N:11]=[C:12]([CH3:13])[C:5]=12.C(N(CC)CC)C.Br.Br[CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1>CN(C)C=O>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH:14]([C:16]3[CH:17]=[C:18]([Cl:30])[C:19]([C:28]#[N:29])=[C:20]4[C:26]=3[O:25][CH:24]([CH3:27])[CH2:23][N:22]([CH2:40][C:41]3[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=3)[CH2:21]4)[CH3:15])[N:11]=[C:12]([CH3:13])[C:5]=12
Reactant: BrCc1cccnc1
Reactant: Cc1nn(C(C)c2cc(Cl)c(C#N)c3c2OC(C)CNC3)c2ncnc(N)c12
Agent: Br
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1nn(C(C)c2cc(Cl)c(C#N)c3c2OC(C)CN(Cc2cccnc2)C3)c2ncnc(N)c12
Temperature: 85 °C

Procedure:
9-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-2-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride (0.020 g, 0.05 mmol) was taken up in N,N-dimethylformamide (2.0 mL) and triethylamine (0.034 mL, 0.24 mmol), and the 3-(bromomethyl)pyridine hydrobromide was added. The reaction was heated to 85° C. for 2 h and was allowed to cool. The product was purified by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two diastereomers: Peak #1 (Example 59): LCMS calculated for C25H26ClN8O (M+H)+: m/z=489.2; found: 489.2; Peak #2 (Example 60): LCMS calculated for C25H26ClN8O (M+H)+: m/z=489.2; found: 489.2.
Reaction SMILES: C(OC(=O)[N:7]([CH2:33][C:34]1[CH:43]=[CH:42][C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=1)[CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)=[CH:18][C:17]2=[O:32])[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+].[ClH:57].C(OCC)(=O)C>C(Cl)(Cl)Cl>[ClH:57].[O:38]1[C:37]2[CH:42]=[CH:43][C:34]([CH2:33][NH:7][CH:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]4[C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[C:19]([C:26]5[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=5)=[CH:18][C:17]4=[O:32])[CH2:10][CH2:9]3)=[CH:35][C:36]=2[O:41][CH2:40][CH2:39]1
Reactant: CC(C)(C)OC(=O)N(Cc1ccc2c(c1)OCCO2)C1CCN(CCn2c(=O)cc(-c3ccncc3)c3ccccc32)CC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: O=c1cc(-c2ccncc2)c2ccccc2n1CCN1CCC(NCc2ccc3c(c2)OCCO3)CC1
Reaction time: 3.5 h

Procedure:
To 1 mL of a chloroform solution containing 42 mg of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(2-oxo-4-(pyridin-4-yl)quinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate, 1 mL of trifluoroacetic acid was added at room temperature and stirred for 3.5 hours, thereafter the solvent was removed under reduced pressure. To the residue thus obtained, chloroform and aqueous saturated sodium hydrogen carbonate solution were added, the organic layer was separated and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. To the residue thus obtained, 1 mL of 4 mol/L hydrogen chloride/ethyl acetate was added, the resulting solid was filtered to give 21 mg of (1-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-4-(pyridin-4-yl)quinolin-2(1H)-one hydrochloride as a pale yellow solid.
Reaction SMILES: [CH3:1][O:2][CH:3]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][O:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:6]=1>CCOC(C)=O.[Pd]>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][O:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:6]=1
Reactant: COC=Cc1cccc(COC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COCCc1cccc(COC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Yield: 65 %

Procedure:
A stirred solution of (methoxymethyl)triphenylphosphonium chloride (2.79 g, 8.13 mmol) in THF (50 mL) at 0° C. was treated dropwise with n-BuLi (1.6-M in hexanes, 5.08 mL, 8.13 mmol), stirred for 1 h, treated with a solution of 6-(triphenylmethoxy)methylpyridine-2-carboxaldehyde (1.54 g, 4.06 mmol) in THF (15 mL) and allowed to warm to room temperature overnight. The reaction was treated with saturated NH4Cl solution (5 mL), diluted with water (50 mL), extracted with EtOAc (2×50 mL) and the combined organic phase diluted with iso-hexane (50 mL), dried (MgSO4), filtered through silica and concentrated in vacuo to give 2-(2-methoxyethenyl)-6-(triphenylmethoxy)methylpyridine (1.58 g) as a yellow oil. A solution of this crude alkene and 10% Pd/C (216 mg, 0.203 mmol) in EtOAc (50 mL) was stirred under a hydrogen atmosphere for 16 h, filtered through Celite and concentrated in vacuo to give the title compound (1.08 g, 65%) as a yellow oil; NMR δH (400 MHz, CDCl3) 7.67-7.64 (1H, m), 7.52-7.49 (6H, m), 7.32-7.21 (10H, m), 7.09-7.07 (1H, m), 4.34 (2H, s), 3.69 (2H, t, J 6.5 Hz), 3.32 (3H, s) and 2.98 (2H, t, J 6.5 Hz); M/Z 410 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[C:9]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[N:10][O:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[C:27]1([CH2:33][CH2:34][CH2:35]Br)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(OCC)(=O)C>CN(C=O)C.CCCCCC>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[C:9]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:35][CH2:34][CH2:33][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:17][CH:18]=2)=[N:10][O:11][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1conc1-c1ccc(O)cc1
Reactant: BrCCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC(C)(C)OC(=O)Nc1conc1-c1ccc(OCCCc2ccccc2)cc1
Temperature: 50 °C
Reaction time: 14 h

Procedure:
To a solution of [3-(4-hydroxy-phenyl)-isoxazol-4-yl]-carbamic acid tert-butyl ester (38 mg, 0.137 mmol) in DMF (1 mL) was added K2CO3 (20 mg, 0.145 mmol) and 3-phenyl-1-bromopropane (20 μL, 0.132 mmol). After stirring for 1 h at rt and 14 h at 50° C., the reaction mixture was cooled stirred for 6 h at rt. The reaction mixture was loaded directly onto silica gel. {3-[4-(3-Phenyl-propoxy)-phenyl]-isoxazol-4-yl}-carbamic acid tert-butyl ester was isolated as a white solid by column chromatography (10% ethyl acetate in hexane).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](Br)=[CH:4][N:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1>>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:5]2[CH:6]=[C:7]([CH3:8])[C:2]([NH2:1])=[N:3][CH:4]=2)=[CH:13][CH:12]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: Cc1cc(Br)cnc1N
Product: Cc1cc(-c2ccc(Cl)cc2)cnc1N
Yield: 82.5 %

Procedure:
Prepared as described in example C.32 (step 4) from commercially available 2-amino-5-bromo-3-methyl-pyridine (4 g, 21.4 mmol) and commercially available 4-chlorophenylboronic acid (3.68 g, 23.5 mmol). Obtained as an off-white solid (3.86 g, 83%). MS (EI) 218.1 [(M)+]; mp 156° C.
Reaction SMILES: C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:7][N:6]1[S:20]([C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1)(=[O:22])=[O:21])=O.O.[NH2:34][NH2:35]>CO>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][S:10][C@H:8]2[CH2:7][N:6]([S:20]([C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:24]=3)(=[O:22])=[O:21])[C@H:5]([C:3]([NH:34][NH2:35])=[O:2])[CH2:9]2)=[CH:13][CH:14]=1
Reactant: NN
Reactant: COC(=O)[C@@H]1C[C@@H](SCc2ccc(OC)cc2)CN1S(=O)(=O)c1ccc2ccccc2c1
Solvent: CO
Solvent: O
Product: COc1ccc(CS[C@@H]2C[C@@H](C(=O)NN)N(S(=O)(=O)c3ccc4ccccc4c3)C2)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
(step 8) To a solution of 5 g (10.6 mmol, 1 eq) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methyl ester in 20 ml methanol were added 6.45 ml (110 mmol, 10 eq) hydrazine-hydrate and the solution was stirred at RT for 3 days. The solvent was evaporated, followed by solving and evaporating with EtOH, ether and hexane. The light yellow solid was dried in vacuo giving (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid hydrazide, mp 130° C., MS: 472 (MH+).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.[NH:30]1[C:38]2[C:33](=[CH:34][C:35](B(O)O)=[CH:36][CH:37]=2)[CH:32]=[CH:31]1>>[NH:30]1[C:38]2[C:33](=[CH:34][C:35]([O:1][C:2]3[CH:3]=[C:4]([C:8]4[C:17]5[C:12](=[C:13]([C:18]([F:21])([F:19])[F:20])[CH:14]=[CH:15][CH:16]=5)[N:11]=[CH:10][C:9]=4[C:22]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[O:23])[CH:5]=[CH:6][CH:7]=3)=[CH:36][CH:37]=2)[CH:32]=[CH:31]1
Reactant: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Reactant: OB(O)c1ccc2[nH]ccc2c1
Product: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(Oc2ccc3[nH]ccc3c2)c1

Procedure:
The title compound was prepared from [4-(3-hydroxy-phenyl)-8-trifluoromethylquinolin-3-yl]-phenyl methanone and 5-Indolylboronic acid, following the procedure of Example 519: MS m/z 509; MS m/z 507.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C@@H:17]([O:38][Si](C(C)(C)C)(C)C)[CH2:18][C@@H:19]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)=[O:29])[CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([NH:8][C@H:9]([C@@H:17]([OH:38])[CH2:18][C@@H:19]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)=[O:29])[CH2:20][C:21]1[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@H](C[C@H](Cc1ccncc1)NC(=O)OCc1cccnc1)O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccncc1)NC(=O)OCc1cccnc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 84.4 %

Procedure:
A solution of 74.5 mg (0.117 mmol) of (2S,3S,5S)-2-(Boc-amino)-5-(N-((3-pyridinyl)methoxycarbonyl)amino)-1-phenyl-6-(4-pyridinyl)-3-(tert-butyldimethylsilyloxy)-hexane in 4 ml of tetrahydrofuran was treated with 102 μl of 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran. After being stirred at ambient temperature for 24 h, the solvent was removed in vacuo, and the residue was purified by silica gel chromatography using 10% methanol in dichloromethane to provide 51.4 mg (84%) of the desired compound as a white solid. 1H NMR (CDCl3) δ 1.37 (s, 9H), 1.65 (t, 2H), 2.82-3.01 (m, 5H), 3.70 (m, 2H), 4.03 (m, 1H), 4.78 (d, 1H), 5.03 (s, 2H), 5.18 (br d, 1H), 7.06 (d, 2H), 7.16-7.31 (m, 6H), 7.61 (d, 1H), 8.44 (d, 2H), 8.57 (s , 2H). Mass spectrum: (M+H)+ 521.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]([O:11][C:12]([N:14]1[CH:18]=[CH:17][CH:16]=[C:15]1B(O)O)=[O:13])([CH3:10])([CH3:9])[CH3:8].O1CCOCC1.[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[C:33](Br)[CH:34]=1>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.C(OCC)(=O)C.O>[C:7]([O:11][C:12]([N:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C:33]1[CH:32]=[N:31][CH:30]=[C:29]([Br:28])[CH:34]=1)=[O:13])([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)OC(=O)n1cccc1B(O)O
Reactant: Brc1cncc(Br)c1
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: [Cs+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)n1cccc1-c1cncc(Br)c1
Temperature: 25 °C
Yield: 53.5 %

Procedure:
Cesium carbonate (165 mg), 1-(tert-butoxycarbonyl)-1H-pyrrol-2-ylboronic acid (136 mg) and Pd(PPh3)4 (24 mg) were added to a 1,4-dioxane (4 ml) solution containing 3,5-dibromopyridine (100 mg), followed by reflux for 4 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic layer was collected, washed with saturated saline, and dried over anhydrous sodium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (silica gel: silica gel 60 (spherical shape) (Kanto Chemical Co., Inc.); hexane:ethyl acetate=4:1), and a white solid of tert-butyl2-(5-bromopyridin-3-yl)-1H-pyrrol-1-carboxylate (73 mg) was thus obtained.
Reaction SMILES: [C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:27])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24]O)[CH3:19])[CH2:12][CH2:11]1.[NH2:34][C:35]1[CH:47]=[CH:46][C:38]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[CH:37][CH:36]=1>>[C:42]([O:41][C:39](=[O:40])[C:38]1[CH:46]=[CH:47][C:35]([NH:34][CH2:24][CH2:23][CH2:22][CH2:21][C:20]([N:18]([CH2:17][CH2:16][N:13]2[CH2:12][CH2:11][CH:10]([O:9][C:8](=[O:27])[NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:15][CH2:14]2)[CH3:19])=[O:26])=[CH:36][CH:37]=1)([CH3:43])([CH3:44])[CH3:45]
Reactant: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCO
Reactant: CC(C)(C)OC(=O)c1ccc(N)cc1
Product: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCNc1ccc(C(=O)OC(C)(C)C)cc1
Yield: 77.3 %

Procedure:
The compound (242 mg, 0.534 mmol) obtained in Example 31a was used to give a crude aldehyde compound (252 mg) according to the method described in Example 4g. The resulting crude aldehyde compound and tert-butyl 4-aminobenzoate (92 mg, 0.475 mmol) were used to give the title compound (231 mg; yield, 69%) as a white solid according to the method described in Example 18b.
Reaction SMILES: [Cl-:1].[CH3:2][N+:3]([CH3:20])([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([NH2:19])[CH:12]=1)[CH2:4][CH2:5][CH2:6][NH:7]C=O.[Cl-].C[N+](C)([CH2:28][C:29]1[CH:34]=[CH:33][C:32](OC)=[C:31]([NH2:37])[CH:30]=1)CCCN.[NH2:39]C1C=CC=C(C)C=1>>[Cl-:1].[CH3:2][N+:3]([CH3:20])([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([N:19]=[N:39][C:34]2[CH:33]=[CH:32][C:31]([NH2:37])=[CH:30][C:29]=2[CH3:28])[CH:12]=1)[CH2:4][CH2:5][CH2:6][NH2:7]
Reactant: Cc1cccc(N)c1
Reactant: COc1ccc(C[N+](C)(C)CCCNC=O)cc1N
Reactant: COc1ccc(C[N+](C)(C)CCCN)cc1N
Agent: [Cl-]
Product: COc1ccc(C[N+](C)(C)CCCN)cc1N=Nc1ccc(N)cc1C

Procedure:
Proceeding in a manner similar to that described above in Example 3, N,N-dimethyl-N-(3-amino-4-methoxybenzyl)-N-3-formamidopropylammonium chloride was hydrolyzed and the resulting N,N-dimethyl-N-(3-amino-4-methoxybenzyl)-N-3-aminopropylammonium chloride was diazotized and coupled with meta-toluidine to obtain N,N-dimethyl-N-[3-(4-amino-2-methylphenyl)azo-4-methoxybenzyl]-N-3-aminopropylammonium chloride in aqueous solution. This product was diazotized in situ and coupled with 4'-chloroacetoacetanilide to obtain the yellow, water-soluble dyestuff having the formula ##STR97##
Reaction SMILES: [NH2:1][C:2]1[CH:29]=[CH:28][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:27])[N:14]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[N:15]=[C:16]([CH:19]([CH3:21])[CH3:20])[C:17]=3[OH:18])=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.C(N(CC)CC)C.[C:37](Cl)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.CN(C=O)C>[OH:18][C:17]1[C:16]([CH:19]([CH3:21])[CH3:20])=[N:15][N:14]([CH2:22][CH2:23][CH:24]([CH3:25])[CH3:26])[C:13](=[O:27])[C:12]=1[C:7]1[NH:6][C:5]2[CH:28]=[CH:29][C:2]([NH:1][C:37](=[O:44])[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:3][C:4]=2[S:9](=[O:10])(=[O:11])[N:8]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)CCn1nc(C(C)C)c(O)c(C2=NS(=O)(=O)c3cc(N)ccc3N2)c1=O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)CCn1nc(C(C)C)c(O)c(C2=NS(=O)(=O)c3cc(NC(=O)c4ccccc4)ccc3N2)c1=O
Temperature: 80 °C
Reaction time: 4 h
Yield: 52.1 %

Procedure:
To a solution of 5j (0.048 g, 0.11 mmol) and 4-dimethylaminopyridine (0.0014 g, 0.011 mmol) in DMF was added triethylamine (18 μL, 0.125 mmol) followed by benzoyl chloride (16 μL, 0.137 mmol). The reaction mixture was stirred 4 h at 80° C. and cooled to room temperature. The reaction mixture was treated with sat NaHCO3 (1 mL) and extracted two times with EtOAc (3 mL). The combined organic layer was washed with brine (1 mL), dried over MgSO4, and concentrated in vacuo. The crude mixture was purified by flash column chromatography using silica gel (0-40% EtOAc/hexanes) to give 5k (0.030 g, 50%) as a yellow solid. 1H NMR (400 MHz, D6-DMSO) δ 10.63 (br s), 8.45 (d, J=2.4 Hz, 1H), 8.09 (dd, J=8.8, 2 Hz, 1 H), 8.97 (d, J=7.2 Hz, 2 H), 7.67 (d, J=9.2 Hz, 1 H), 7.60 (d, J=7.2 Hz, 1 H), 7.54 (t, J=7.2 Hz, 2 H), 4.13 (d, J=6.8 Hz, 2 H), 3.25 (m, 1 H), 1.63 (m, 3 H), 1.22 (d, J=6.8 Hz, 6 H), 0.93 (d, J=6.4 Hz, 6 H). LC-MS(ESI+) m/e 524 [M+H]+.
Reaction SMILES: N1C=CC=CC=1.[CH3:7][NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)(OC(Cl)(Cl)Cl)[O:17][C:18]([Cl:21])(Cl)Cl.Cl>C(Cl)Cl>[CH2:9]([N:8]([CH3:7])[C:18]([Cl:21])=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CNCc1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CN(Cc1ccccc1)C(=O)Cl
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
At −78° C. pyridine (1.25 mL, 15.5 mmol) followed by methyl benzylamine (2.0 mL, 15.5. mmol) are added to a solution of bis(trichloromethyl) carbonate (1.55 g, 5.2 mmol) in CH2Cl2 (20 mL). The reaction mixture is allowed to warm to RT and stirred for another 1.5 h. For workup 1N HCl is added to the yellow suspension and the mixture is extracted with ethyl acetate. Drying (Na2SO4) of the combined organic exctracts, filtration and evaporation of the solvent affords the title compound. MS (LC-MS): [M+H]+=184.1. tR (HPLC, Waters Symmetry C18 column, 20-95% CH3CN/H2O/3.5 min, 95% CH3CN/H2O, 2 min, CH3CN and H2O containing 0.1% TFA, flow: 0.6 mL/min): 3.84 min.
Reaction SMILES: [CH2:1]([N:8]1[C:12](=[O:13])[C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[Se:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[SH:18][CH2:19][C:20]([OH:22])=[O:21]>>[CH2:1]([NH:8][C:12]([C:11]1[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=1[Se:9][S:18][CH2:19][C:20]([OH:22])=[O:21])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=c1c2ccccc2[se]n1Cc1ccccc1
Reactant: O=C(O)CS
Product: O=C(O)CS[Se]c1ccccc1C(=O)NCc1ccccc1

Procedure:
Prepared similar to example 1 from 2,88 g (10,0 mmol) of 2-benzyl-1,2-benzisoselenazole-3(2H)-one and 0,95 g (10,3 mmol) mercaptoactic acid.
Reaction SMILES: [C:1]([C:4]1[C:5]([O:23][CH3:24])=[C:6]([CH:12]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]2)[C:7]([F:11])=[C:8]([Cl:10])[CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO.O>[Cl:10][C:8]1[C:7]([F:11])=[C:6]([CH:12]2[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]2)[C:5]([O:23][CH3:24])=[C:4]([CH:1]([OH:3])[CH3:2])[CH:9]=1
Reactant: COc1c(C(C)=O)cc(Cl)c(F)c1C1CN(C(=O)OC(C)(C)C)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1c(C(C)O)cc(Cl)c(F)c1C1CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 110 %

Procedure:
To a solution of tert-butyl 3-(3-acetyl-5-chloro-6-fluoro-2-methoxyphenyl)azetidine-1-carboxylate (0.17 g, 0.48 mmol) in methanol (3 mL) cooled at 0° C. was added sodium tetrahydroborate (0.022 g, 0.57 mmol). The mixture was stirred at room temperature for 1 hour, then diluted with water and extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated to give the desired product (0.19 g). LCMS calculated for C17H23ClFNO4Na (M+Na)+: m/z=382.1. found: 382.0.