Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14](O)=[O:15]>CCCCCCC.C(OCC)(=O)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15]
Reactant: COCCCCCCCCCCCC(=O)O
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: COCCCCCCCCCCCCO
Yield: 78.2 %

Procedure:
The title compound was prepared by the method of Example 3 using the title product of Example 1 (3 g, 13 mmol) instead of the title product of Example 2. Chromatography by of the crude residue on silica gel using 50--50 ethyl acetate heptane gave the title compound (2.2 g) as a white powder, m.p. 32.6°-36.7° C. (DSC). The structure was supported by NMR, infrared spectroscopy, elemental analysis and mass spectroscopy.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:28]C)[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2O)=[N:13][C:14]=1[CH2:15]C.Br[C:31]1N=C(C)C(NC2C3C(=CC=CC=3)CCC2)=NC=1C>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH3:28])[C:12]([NH:17][CH:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:31][CH2:19]2)=[N:13][C:14]=1[CH3:15]
Reactant: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@@H]1O
Reactant: Cc1nc(NC2CCCc3ccccc32)c(C)nc1Br
Product: Cc1nc(-c2ccc(Cl)cc2Cl)c(C)nc1NC1CCCc2ccccc21

Procedure:
Following the procedure for the preparation of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol but substituting Preparation of 5-bromo-3,6-dimethyl-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyrazin-2-amine and making non-critical variations provided the title compound as a oil: 1H NMR (CDCl3) δ 1.95, 2.15, 2.28, 2.35, 2.90, 4.62, 5.52, 7.23, 7.34, 7.41, 7.51; MS (ESI+) for C22H21Cl3N3 m/z 399.1 (M+H)+.
Reaction SMILES: C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16][CH2:17][O:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[C:10]=1[CH2:24][CH3:25])C1C=CC=CC=1.CCO.CCOC(C)=O>CN(C)C=O.[Pd]>[CH2:24]([C:10]1[N:11]([CH2:16][CH2:17][O:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[CH:12]=[CH:13][C:14](=[O:15])[C:9]=1[OH:8])[CH3:25]
Reactant: CCc1c(OCc2ccccc2)c(=O)ccn1CCOC(=O)C(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CN(C)C=O
Product: CCc1c(O)c(=O)ccn1CCOC(=O)C(C)C
Reaction time: 96 h
Yield: 37 %

Procedure:
3-Benzyloxy-2-ethyl -1-[2-(α-methylpropionyloxy)ethyl]pyridin-4-one was dissolved in 35 ml of dimethylformamide and about 0.1 g of palladium on activated charcoal (5%) was added. The solution was left under H2 for four days and the reaction was monitored by tlc (silica; 50% EtOH:50% EtOAc). The solution was filtered three times and rotary evaporated under high vacuum. The oily residue was then treated with activated charcoal in ethyl acetate, filtered and rotary evaporated to dryness. After crystallization from ethyl acetate the pure title compound was obtained in 37% yield, m.p., i.r., n.m.r. and mass spectra as quoted in Example 4.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[NH:14][C@H:13]2[CH3:18])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[H-].[Na+].CS(O[CH2:26][C:27]1[C:32]([C:33]2[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[C:36]([F:42])=[CH:35][C:34]=2[O:43][CH3:44])=[CH:31][N:30]=[C:29]([S:45][CH3:46])[N:28]=1)(=O)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[N:14]([CH2:26][C:27]3[C:32]([C:33]4[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[C:36]([F:42])=[CH:35][C:34]=4[O:43][CH3:44])=[CH:31][N:30]=[C:29]([S:45][CH3:46])[N:28]=3)[C@H:13]2[CH3:18])[CH:5]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:7]=1
Reactant: COc1cc(F)c(C(C)C)cc1-c1cnc(SC)nc1COS(C)(=O)=O
Reactant: C[C@@H]1NC(=O)O[C@@H]1c1cc(Br)cc(C(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(F)c(C(C)C)cc1-c1cnc(SC)nc1CN1C(=O)O[C@H](c2cc(Br)cc(C(F)(F)F)c2)[C@@H]1C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 67(c)—(Table 8), 145 mg, 0.447 mmol) in THF (4 mL) at 0° C. was added sodium hydride (60 wt %, 23.3 mg, 0.582 mmol). The reaction was stirred at 0° C. for 1 hour and a solution of {5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-2-(methylsulfanyl)pyrimidin-4-yl}methyl methanesulfonate (188 mg, 0.470 mmol) in THF (500 μL) was added. The reaction was allowed to warm to room temperature and was stirred at room temperature for 6 hours. The reaction was quenched with HCl (1 N) and the reaction was poured into saturated aqueous NaHCO3 and ethyl acetate. The organic was washed with brine, was dried (Na2SO4), filtered, and concentrated. The resultant residue was purified by column chromatography to yield (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-3-({5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-2-(methylsulfanyl)pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (190 mg, 0.302 mmol). LCMS calc.=628.1/630.1. found=628.2/630.2
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:15]([NH2:17])=[O:16].NC1N=C(C2C(Cl)=CC=CN=2)C=CC=1C(N)=O.[C:35](OCC)(=O)[C:36]([O:38][CH2:39][CH3:40])=[O:37]>>[CH2:39]([O:38][C:36]([C:35]1[N:17]=[C:15]([OH:16])[C:3]2[CH:4]=[CH:5][C:6]([C:8]3[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=3)=[N:7][C:2]=2[N:1]=1)=[O:37])[CH3:40]
Reactant: CCOC(=O)C(=O)OCC
Reactant: Cc1cccnc1-c1ccc(C(N)=O)c(N)n1
Agent: NC(=O)c1ccc(-c2ncccc2Cl)nc1N
Product: CCOC(=O)c1nc(O)c2ccc(-c3ncccc3C)nc2n1
Temperature: 160 °C

Procedure:
Dissolve 6-amino-3′-methyl-[2,2′]bipyridinyl-5-carboxylic acid amide (1.00 g, 4.38 mmol, prepared in a manner analogous to that described above for the preparation of 6-amino-3′-chloro-[2,2′]bipyridinyl-5-carboxylic acid amide) in diethyl oxalate (24 mL) and heat the mixture at 160° C. for 8 hours or until all starting material is gone as indicated by TLC. Pour the hot mixture onto ice and extract with CH2Cl2 (2×100 mL). Dry the combined organic extracts over Na2SO4. Remove the solvent under reduced pressure. Chromatograph the crude product on silica gel eluting first with CH2Cl2 followed by CH2Cl2/MeOH (95:5) to yield the title compound. MS 311.12 (M+1).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[OH:13])([O-:3])=[O:2].[CH3:14][O:15][CH2:16]Cl.O>CN(C=O)C>[CH3:14][O:15][CH2:16][O:13][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:4]=1[N+:1]([O-:3])=[O:2])[CH2:10][CH2:9][CH2:8]2
Reactant: O=[N+]([O-])c1cc2c(cc1O)CCC2
Reactant: COCCl
Solvent: CN(C)C=O
Solvent: O
Product: COCOc1cc2c(cc1[N+](=O)[O-])CCC2
Temperature: 5 °C
Reaction time: 0.25 h

Procedure:
1.04 g of 55% sodium hydride/paraffin oil was suspended in 40.0 mL of DMF, and a solution of 3.90 g of 6-nitroindan-5-ol in DMF (10.0 mL) was added dropwise thereto at 5° C. over 15 minutes, followed by stirring at 5° C. for 30 minutes. To the reaction liquid was added dropwise 2.15 mL of methoxymethyl chloride over 5 minutes, followed by stirring at room temperature for 1 hour. To the reaction liquid was added water, followed by extraction with ethyl acetate, and the organic layer was washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 80:20) to obtain 4.20 g of 5-(methoxymethoxy)-6-nitroindane.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:24]C)=[C:4]([O:22]C)[CH:5]=[C:6]([CH:8]=[CH:9][C:10]2[CH:15]=[C:14]([O:16]C)[C:13]([O:18]C)=[C:12]([O:20]C)[CH:11]=2)[CH:7]=1.Cl.N1C=CC=CC=1.[K+].[Br-]>>[Br:1][C:2]1[C:3]([OH:24])=[C:4]([OH:22])[CH:5]=[C:6](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[C:14]([OH:16])[C:13]([OH:18])=[C:12]([OH:20])[CH:11]=2)[CH:7]=1
Reactant: COc1cc(C=Cc2cc(OC)c(OC)c(OC)c2)cc(Br)c1OC
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: c1ccncc1
Product: Oc1cc(/C=C/c2cc(O)c(O)c(Br)c2)cc(O)c1O

Procedure:
Demethylation: The 1-(5-bromo-3,4-dimethoxyphenyl)-2-(3,4,5-trimethoxyphenyl) ethylene (1.3 g) on demethylation with pyridine hydrochloride (7 g) under the conditions noted in example 1 gave 2, m.p. 148° C.; IR (KBr) νmax 3450, 1610, 1536, 1461, 1431, 1340, 1291, 1191, 1038, 997, 954, 842, 799 cm−1; 1H NMR (DMSO-d6, 400 MHz) δ 9.81 (1H, s), 9.21 (1H, s), 8.88 (2H, s), 8.30 (1H, s), 7.13 (1H, s), 6.93 (1H, s), 6.72 (1H, d, J=16.2 Hz), 6.64 (1H, d, J=16.2 Hz), 6.47 (2H, s).
Reaction SMILES: C(OC)(=O)C[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10](OC)=O.[OH2:17]>>[C:5]1([C@@H:4]([OH:17])[CH3:3])[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: O
Reactant: COC(=O)CCCCCCCCC(=O)OC
Product: C[C@H](O)c1ccccc1

Procedure:
Interesterification was carried out in the same manner as in Example 12, except for replacing dimethyl octadecadicarboxylate with 150 g of dimethyl sebacate at 90° C. for 30 hours. The water content of the reaction system was 0.07% by weight, and 87% of the lipase particles had a particle size of 25 to 60 μm. After completion of the reaction, gas chromatography of the reaction mixture revealed that 42 mol % of (R,S)-1-phenylethanol had been converted to its sebacic acid ester. The reaction mixture was treated in the same manner as in Example 12 to remove lipase, and the filtrate was subjected to simple distillation at 90° C. and 3 mmHg. However, it was impossible to isolate (S)-(-)-1-phenylethanol due to co-distillation of other components, such as esters.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21](Cl)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[C:29]([NH:42][C:43]2[CH:48]=[CH:47][N:46]=[CH:45][N:44]=2)[C:28]1=[O:49].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(#N)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:31]3[CH:30]=[C:29]([NH:42][C:43]4[CH:48]=[CH:47][N:46]=[CH:45][N:44]=4)[C:28](=[O:49])[N:27]([CH3:26])[CH:32]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1cc(F)c2c(=O)n(-c3nccc(Cl)c3C=O)ncc2c1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cc(Nc2ccncn2)c1=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=P([O-])([O-])[O-]
Solvent: O
Solvent: CC#N
Product: Cn1cc(-c2ccnc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c2C=O)cc(Nc2ccncn2)c1=O
Temperature: 100 °C
Yield: 49.1 %

Procedure:
A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (110 mg, 0.31 mmol), 113b (100 mg, 0.31 mmol), PdCl2(dppf) (25 mg, 0.030 mmol), K3PO4 (241 mg, 0.93 mmol), NaAcO (76 mg, 0.93 mmol), acetonitrile (15 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 113c as a red solid (80 mg, 51%). MS-ESI: [M+H]+ 526.3
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]=2Cl)=[O:9])[CH2:4][CH2:3]1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[C:31]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)=[O:32].Cl>>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]=2[N:36]2[CH2:37][CH2:38][N:33]([C:31](=[O:32])[C:30]3[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:28]([O:27][CH3:26])[CH:29]=3)[CH2:34][CH2:35]2)=[O:9])[CH2:4][CH2:3]1
Reactant: COc1cc(C(=O)N2CCNCC2)cc(OC)c1OC
Reactant: CN1CCN(C(=O)c2c(Cl)n(-c3ccccc3)c3ccccc23)CC1
Agent: Cl
Product: COc1cc(C(=O)N2CCN(c3c(C(=O)N4CCN(C)CC4)c4ccccc4n3-c3ccccc3)CC2)cc(OC)c1OC

Procedure:
This compound was prepared from 2-chloro-1-phenyl-indole 3-carboxylic acid 4-methyl-piperazide and 3,4,5-trimethoxy benzoic acid piperazide in boiling diglym according to Examples 7, 40, 42 and 45. The yield of amorphous product amounted to 77% of the theoretical yield. The hydrochloride melted at 253°-255° C.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([Cl:12])=[N:7]2.[Li+].[CH3:14]C([N-]C(C)C)C.IC.[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH3:14])[C:6]([Cl:12])=[N:7]2
Reactant: Clc1ccc2c(Br)cccc2n1
Reactant: CC(C)[N-]C(C)C
Agent: [Cl-]
Agent: [Li+]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CI
Product: Cc1cc2c(Br)cccc2nc1Cl
Reaction time: 1 h

Procedure:
To a solution of 5-bromo-2-chloroquinoline (1.0 g, 4.1 mmol) in anhydrous THF (20 mL) at −78° C. was added LDA (2.0 M in heptane/THF/ethylbenzene, 3.1 mL, 6.2 mmol) dropwise. After stirring for one hour, iodomethane (1.28 mL, 20.6 mmol) was added, and the mixture was stirred at −78° C. for another hour. The mixture was poured into saturated NH4Cl (aq) then extracted twice with EtOAc. The organic extracts were concentrated and the residue was purified by reverse-phase HPLC to afford the title compound: 1H NMR (500 MHz, CDCl3): δ 8.34 (s, 1H); 7.96 (d, J=8.3 Hz, 1H); 7.80 (d, J=7.5 Hz, 1H); 7.53 (d, J=7.8 Hz, 1H); 2.60 (s, 3H) LC3: 1.41 min. (M+H) 258.
Reaction SMILES: Br[C:2]1[C:3](=[O:36])[C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=1)=[CH:8][CH:7]=[C:6]([O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1)[CH:5]=2.O1CCN(CCOC2C=C3C(C(C4C=CC=CC=4)=C(Br)C3=O)=CC=2)CC1.[N:63]1[C:72]2[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=2)[CH:66]=[C:65](B(O)O)[CH:64]=1>>[F:17][C:15]1[CH:16]=[C:11]([C:10]2[C:9]3[C:4](=[CH:5][C:6]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:27][CH2:28]4)=[CH:7][CH:8]=3)[C:3](=[O:36])[C:2]=2[C:65]2[CH:64]=[N:63][C:72]3[C:67]([CH:66]=2)=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH:12]=[C:13]([F:18])[CH:14]=1
Reactant: OB(O)c1cnc2ccccc2c1
Reactant: CC(C)(C)OC(=O)N1CCN(CCCOc2ccc3c(c2)C(=O)C(Br)=C3c2cc(F)cc(F)c2)CC1
Agent: O=C1C(Br)=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc21
Product: CC(C)(C)OC(=O)N1CCN(CCCOc2ccc3c(c2)C(=O)C(c2cnc4ccccc4c2)=C3c2cc(F)cc(F)c2)CC1
Yield: 39 %

Procedure:
The procedure of Step 7 of Example 1 was repeated except for using t-butyl 4-(3-(2-bromo-3-(3,5-difluorophenyl)-1-oxo-1H-inden-6-yloxy)propyl)piperazine-1-carboxylate obtained in Step 1 as a starting material instead of 6-(2-morpholinoethoxy)-2-bromo-3-phenyl-1H-inden-1-one, 3-quinolinylboronic acid instead of 3-pyridinylboronic acid, and being purified by silica gel column chromatography (EtOAc/hexanes=1:1) to obtain the title compound (39%).
Reaction SMILES: [ClH:1].O1CCOCC1.[CH3:8][C:9]1([CH3:38])[C:13]([CH3:15])([CH3:14])[O:12][B:11]([C:16]2[CH:17]=[C:18]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[N:19](C(OC(C)(C)C)=O)[CH:20]=2)[O:10]1>C(Cl)Cl>[CH3:14][C:13]1([CH3:15])[C:9]([CH3:8])([CH3:38])[O:10][B:11]([C:16]2[CH:17]=[C:18]([C:28]([O:30][CH2:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[O:29])[NH:19][CH:20]=2)[O:12]1.[ClH:1]
Reactant: CC(C)(C)OC(=O)n1cc(B2OC(C)(C)C(C)(C)O2)cc1C(=O)OCc1ccccc1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: CC1(C)OB(c2c[nH]c(C(=O)OCc3ccccc3)c2)OC1(C)C
Reaction time: 0.5 h

Procedure:
Hydrogen chloride in 1,4-dioxane (4.0 M, 3.0 mL, 12 mmol) was added to a solution of 2-benzyl 1-tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2-dicarboxylate (0.80 g, 1.9 mmol) in methylene chloride (3.0 mL) at r.t. and the mixture was stirred for 0.5 h. The solvent was removed under reduced pressure to provide the desired product as an HCl salt. LCMS (M+H)+: m/z=328.2.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH3:18])=[O:5])[CH3:2].[Br:19]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH2:18][Br:19])=[O:5])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1sc(Oc2ccccc2)nc1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1sc(Oc2ccccc2)nc1CBr
Temperature: 25 °C
Yield: 101.9 %

Procedure:
A mixture of 4-methyl-2-phenoxy-thiazole-5-carboxylic acid ethyl ester (1.31 g, 4.99 mmol), N-bromosuccinimide (905 mg, 5.08 mmol) and benzoyl peroxide (60 mg, 0.25 mmol) in carbon tetrachloride (25 mL) was refluxed for 3 h before it was cooled to room temperature and partitioned between dichloromethane and water, the organic layer was washed with saturated aqueous sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound as a yellow solid (1.74 g): MS: (+) m/z 342.0, 344.0 (M+1, 79Br/81Br).
Reaction SMILES: [Si]([O:18][CH:19]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])/[CH:20]=[CH:21]/[C:22]1[N:27]=[C:26]([CH:28]=[O:29])[CH:25]=[CH:24][CH:23]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+].C(OCC)(=O)C.[O:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1>>[OH:29][CH:28]([C:26]1[CH:25]=[CH:24][CH:23]=[C:22](/[CH:21]=[CH:20]/[CH:19]([OH:18])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[N:27]=1)[CH2:50][CH2:49][CH2:48][CH2:47][OH:46]
Reactant: CCCCCCCCC(/C=C/c1cccc(C=O)n1)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: C1CCOC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Product: CCCCCCCCC(O)/C=C/c1cccc(C(O)CCCCO)n1
Temperature: -80 °C
Reaction time: 2 h

Procedure:
5.1 ml of a Grignard solution (produced from 385 mg of magnesium and 1.76 g of 4-chloro-1-tert-butyldimethylsilyloxybutane in tetrahydrofuran) is instilled at -80° C. in a solution of 370 mg of 6-[(1E)-(3RS)-3-tert-butyldiphenylsilyloxy-1-undecenyl]-pyridine-2-carbaldehyde in 3 ml of tetrahydrofuran. After 2 hours of stirring at -80° C., the reaction mixture is poured into 10 ml of saturated ammonium chloride solution, shaken out with ethyl acetate, the organic phase is dried and concentrated by evaporation. The residue is dissolved in 10 ml of tetrahydrofuran, mixed with 2.47 g of tetrabutylammonium fluoride and stirred for 17 hours at room temperature. The reaction mixture is poured into 50 ml of diethyl ether, washed with saturated common salt solution, dried on sodium sulfate and concentrated by evaporation. The residue is chromatographed on silica gel with hexane/0-30% ethyl acetate. 110 mg of the title compound is obtained as yellow oil.
Reaction SMILES: [C:1]1([N:7]([CH2:30][CH2:31][CH2:32][C:33]([O:35][C:36](C)(C)C)=[O:34])[C:8]([C:10]2[CH:29]=[CH:28][C:13]3[N:14]([CH3:27])[C:15]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:40].C(=O)([O-])[O-].[NH4+:45].[NH4+]>CO>[ClH:40].[ClH:40].[C:1]1([N:7]([CH2:30][CH2:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])[C:8]([C:10]2[CH:29]=[CH:28][C:13]3[N:14]([CH3:27])[C:15]([CH2:17][CH2:18][C:19]4[CH:20]=[CH:21][C:22]([C:25](=[NH:26])[NH2:45])=[CH:23][CH:24]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [NH4+]
Reactant: Cn1c(CCc2ccc(C#N)cc2)nc2cc(C(=O)N(CCCC(=O)OC(C)(C)C)c3ccccc3)ccc21
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Product: COC(=O)CCCN(C(=O)c1ccc2c(c1)nc(CCc1ccc(C(=N)N)cc1)n2C)c1ccccc1
Yield: 83.5 %

Procedure:
Prepared analogously to Example 25d from 1-methyl-2-[2-(4-cyanophenyl)ethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(3-tert.butyloxycarbonylpropyl)-amide and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 83.5% of theory, Rf value: 0.17 (silica gel; dichloromethane/ethanol=4:1) C29H31N5O3 (497.6) ##EQU15##
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:12]([C@@H:13]([OH:29])[CH2:14][C@H:15]([C:19](=[O:28])[NH:20][CH2:21][C:22]([C:25](=[O:27])[NH2:26])([CH3:24])[CH3:23])[CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([CH:30]([CH3:32])[CH3:31])[C@@H:9]1[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[C:35]([O:41][CH2:42][CH2:43][CH2:44][O:45][CH3:46])[CH:34]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N.[Li].[Cl-].[NH4+]>O1CCCC1.C(O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:12]([CH2:11][C@H:10]([CH2:9][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[C:35]([O:41][CH2:42][CH2:43][CH2:44][O:45][CH3:46])[CH:34]=1)[CH:30]([CH3:32])[CH3:31])[C@@H:13]([OH:29])[CH2:14][C@H:15]([C:19](=[O:28])[NH:20][CH2:21][C:22]([C:25](=[O:27])[NH2:26])([CH3:23])[CH3:24])[CH:16]([CH3:17])[CH3:18])([CH3:2])([CH3:3])[CH3:4]
Reactant: COCCCOc1cc([C@H]2[C@H](C(C)C)C[C@@H]([C@@H](O)C[C@H](C(=O)NCC(C)(C)C(N)=O)C(C)C)N2C(=O)OC(C)(C)C)ccc1OC
Agent: N
Agent: [Cl-]
Agent: [Li]
Solvent: C1CCOC1
Solvent: CCO
Product: COCCCOc1cc(C[C@@H](C[C@H](NC(=O)OC(C)(C)C)[C@@H](O)C[C@H](C(=O)NCC(C)(C)C(N)=O)C(C)C)C(C)C)ccc1OC
Temperature: -78 °C
Reaction time: 2 h

Procedure:
A solution of 0.037 g of amide 12 is dissolved in 1 mL of tetrahydrofurane and cooled to −78° C. Liquid ammonia is added followed by 0.0042 g of lithium metal. The deep blue solution is stirred for 2 hours at −78° C., and then 0.35 g of ethanol is added and the mixture is stirred for 30 minutes at −78° C. Ammonium chloride (0.15 g) is added and the mixture is warmed to room temperature. The organic phase is partitioned between water and ethyl acetate. The organic phase is separated and the solvent removed in vacuum. The residue is stirred with heptane and filtered. Removal of the heptane produces 13 identical with an authentic sample. M++H=652
Reaction SMILES: [CH3:1][N:2]([CH3:10])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][OH:9].[H-].[Na+].O.[CH3:14][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18]Cl>O1CCCC1.CN(C)C=O>[CH3:14][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18][O:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:10])[CH3:1]
Reactant: CN(C)CCCCCCO
Reactant: COc1ccccc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1ccccc1COCCCCCCN(C)C
Reaction time: 0.75 h

Procedure:
6-(Dimethylamino)hexanol (8.80 g, 60.6 mmol) was dissolved in an anhydrous 2:1 mixture of tetrahydrofuran and dimethylformamide (150 mL) and the solution was cooled in an ice bath. Sodium hydride (60% in oil, 3.23 g, 80.8 mmol) was added in portions and after 5 min. the water bath was removed. After 45 min., 2-methoxybenzyl chloride (6.28 g, 40.4 mmol) was added. After 4 h, the reaction mixture was quenched with 1 M sodium thiosulfate and tetrahydrofuran was removed in vacuo. The reaction mixture was washed with ethyl acetate and the aqueous phase was basified with 3 M sodium hydroxide, followed by extraction with ether. The ether layer was dried over potassium carbonate, filtered and acidified with 4 M hydrochloric acid in dioxane. The reaction mixture was concentrated in vacuo and the residue was crystallized form ethanol/ether to give O-(2-methoxybenzyl)-6-dimethylaminohexanol as the hydrochloride salt (10.4 g, 85%). MS (M−Cl)+266.3.