Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[CH2:17][NH:16][CH2:15][CH2:14]2)=[O:10].[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][C:28](O)=[O:29].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl.O.CN(C=O)C.C(N(CC)CC)C>[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][C:28]([N:16]1[CH2:15][CH2:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:9]([NH:8][O:7][CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)=[O:10])[CH:12]=2)[CH2:17]1)=[O:29]
Reactant: O=C(NOC1CCCCO1)c1ccc2c(c1)CCNC2
Reactant: O=C(O)Cc1ccccn1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: O=C(NOC1CCCCO1)c1ccc2c(c1)CCN(C(=O)Cc1ccccn1)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.2 %

Procedure:
A mixture of 200 mg N-(tetrahydro-2H-pyran-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide, 69 mg 2-pyridyl-acetic acid, 111 mg HOBt, 276 mg EDC, 0.603 ml triethylamine and 7 ml DMF is stirred overnight at ambient temperature. The reaction mixture is added to a mixture of 5 ml water and 10 ml dichloromethane. The water phase is washed with dichloromethane and the combined organic phases are dried and evaporated. 80 mg of the title compound are obtained as colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH3:27])[CH:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][N:24]([CH3:26])[CH2:23]4)[CH2:18][CH2:17]3)[CH:8]=2)=[C:4]([F:31])[CH:3]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[F:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54][C:55]([N:57]=[C:58]=[S:59])=[O:56])=[CH:50][CH:49]=1.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.CCCCCC>[F:31][C:4]1[CH:3]=[C:2]([NH:1][C:58]([NH:57][C:55](=[O:56])[CH2:54][C:51]2[CH:52]=[CH:53][C:48]([F:47])=[CH:49][CH:50]=2)=[S:59])[CH:30]=[CH:29][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH3:27])[CH:16]2[CH2:17][CH2:18][N:19]([CH:22]3[CH2:23][N:24]([CH3:26])[CH2:25]3)[CH2:20][CH2:21]2)[CH:8]=1
Reactant: CN1CC(N2CCC(N(C)C(=O)Nc3cc(Oc4ccc(N)cc4F)ncn3)CC2)C1
Reactant: O=C(Cc1ccc(F)cc1)N=C=S
Agent: CC1(C)C2CC[C@@]1(CS(=O)(=O)O)C(=O)C2
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: CCOCC
Product: CN1CC(N2CCC(N(C)C(=O)Nc3cc(Oc4ccc(NC(=S)NC(=O)Cc5ccc(F)cc5)cc4F)ncn3)CC2)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 11 %

Procedure:
To a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-methyl-1-[1-(1-methylazetidin-3-yl)piperidin-4-yl]urea (68.0 mg) in ethanol (2.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (70.2 mg), followed by stirring at room temperature for 10 min. A solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.25 M, 1.91 ml) was added to the reaction mixture, followed by stirring at room temperature for 30 min. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=25:1). Fractions containing the target compound were concentrated to give a residue, to which were added diethyl ether (2 ml) and hexane (2 ml) to give a precipitate. The precipitate was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (10.9 mg, 11.0%) as white powder.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.B(Br)(Br)Br>ClCCl>[C:13]1([CH3:16])[CH:12]=[CH:11][C:10]([O:9][C:6]2[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=2)=[CH:15][CH:14]=1
Reactant: COc1ccc(Oc2ccc(C)cc2)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Cc1ccc(Oc2ccc(O)cc2)cc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 82.7 %

Procedure:
1-methoxy-4-(4-methylphenoxy)benzene (23.50 g, 0.110 mol) was taken into anhydrous dichloromethane (100 mL). The mixture was cooled to −78° C. Boron tribromide (82.43 g, 0.329 mol) in anhydrous dichloromethane (100 mL) was added to the reaction dropwise over 10 min. The reaction was kept at −78° C. for 2 h. and was then allowed to warm to room temperature overnight. The reaction was then cooled to 0° C. and quenched with methanol. The mixture was concentrated to dryness and the residue taken into dichloromethane. The pH was adjusted to 8 with sodium bicarbonate (aq). The mixture was partitioned and the aqueous layer was washed with dicholoromethane (3×). The combined organic layers were washed with water (2×), brine (1×) and concentrated to dryness to obtain the title product (18.29 g, 0.091 mol, 83% yield); LCMS; m/z 200, found 199 (M−H). 1H NMR (400 MHz, DMSO-d6) δ 2.25 (s, 3H), 6.74-6.85 (m, 6H), 7.10-7.13 (m, 2H), 9.28 (s, 1H).
Reaction SMILES: CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=O)=O.[CH3:27][C:28]1([CH3:35])[NH:33][CH2:32][CH2:31][NH:30][C:29]1=[O:34].C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-].O>C(Cl)(Cl)Cl.CC(O)C.C(#N)C>[CH2:20]([N:8]1[CH2:9][CH2:10][N:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:12][C@@H:7]1[CH2:6][N:33]1[CH2:32][CH2:31][NH:30][C:29](=[O:34])[C:28]1([CH3:35])[CH3:27])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC1(C)NCCNC1=O
Reactant: CS(=O)(=O)OC[C@H]1CN(Cc2ccccc2)CCN1Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CC(C)O
Solvent: ClC(Cl)Cl
Product: CC1(C)C(=O)NCCN1C[C@H]1CN(Cc2ccccc2)CCN1Cc1ccccc1
Temperature: 130 °C
Reaction time: 0.5 h
Yield: 59.8 %

Procedure:
A 20 ml, microwave vial was charged with ((2R)-1,4-dibenzyl-2-piperazinyl)methyl methanesulfonate (0.817 g, 2.18 mmol, Example 184, Step 1), 3,3-dimethylpiperazin-2-one (0.297 g, 2.32 mmol, ChemBridge, San Diego, Calif.), potassium carbonate (0.910 g, 6.58 mmol) and acetonitrile (10 mL). The vial was sealed and the reaction mixture was stirred at 130° C. for 30 min. The reaction was allowed to cool to room temperature then saturated aqueous NH4Cl/water (1:1) (100 mL) and 10% iPrOH in chloroform (100 mL) were added. The aqueous phase was extracted with 10% iPrOH in chloroform (2×50 mL). The combined organic phases were washed with saturated aqueous NaCl (200 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 10% iPrOH (with 10% NH4OH) in CHCl3) to afford 4-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.53 g) as a white foam.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C:11](=[O:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[OH-].[Na+]>C(O)C.O.[OH-].[Na+]>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH:10][C:11](=[O:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:4][CH:3]=1
Reactant: CCCCCC(C)=O
Reactant: O=Cc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCCC(=O)C=Cc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
70 ml of water are added to a solution of 90 g (0.64 mol) of 4-chlorobenzaldehyde and 68.5 g (0.6 mol) of 2-heptanone in 300 ml of ethanol and directly thereafter a solution of 1.7 g of sodium hydroxide in 17 ml of water is added. The mixture is initially stirred for 1 hour at room temperature, then 0.6 g of solid sodium hydroxide is added and the mixture is stirred for a further 64 hours. The precipitated product is filtered off with suction, washed with 1 liter of water, pressed out on a clay plate and then dried in vacuo for 16 hours over phosphorus pentoxide. 135 g (95.1% of theory) of 1-(4-chlorophenyl)-1-octen-3-one are obtained in the form of a pale yellow solid of melting point 44°-47° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]([C@@H:18]2[O:32][C@H:31]([CH2:33][O:34]C(C3C(C)=CC=CC=3)=O)[C@@H:20]([O:21]C(C3C(C)=CC=CC=3)=O)[CH2:19]2)[C:4]2[C:9]([C:10]=1[C:11]1[O:12][CH:13]=[CH:14][CH:15]=1)=[CH:8][C:7]([Cl:16])=[C:6]([Cl:17])[CH:5]=2.C[O-].[Na+].CO.C(Cl)(Cl)Cl>CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]([C@@H:18]2[O:32][C@H:31]([CH2:33][OH:34])[C@@H:20]([OH:21])[CH2:19]2)[C:4]2[C:9]([C:10]=1[C:11]1[O:12][CH:13]=[CH:14][CH:15]=1)=[CH:8][C:7]([Cl:16])=[C:6]([Cl:17])[CH:5]=2
Reactant: Cc1ccccc1C(=O)OC[C@H]1O[C@@H](n2c(Cl)c(-c3ccco3)c3cc(Cl)c(Cl)cc32)C[C@@H]1OC(=O)c1ccccc1C
Agent: C[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: OC[C@H]1O[C@@H](n2c(Cl)c(-c3ccco3)c3cc(Cl)c(Cl)cc32)C[C@@H]1O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 75.6 %

Procedure:
2,5,6-Trichloro-3-(2-furyl)-1-(3,5-di-O-toluoyl-2-deoxy-β-D-ribofuranosyl)indole (4.76, 142 mg, 0.22 mmol) was suspended in dry MeOH (10 mL) to which was added sodium methoxide (30 mg, 0.56 mmol). The suspension was stirred at room temperature for 45 min, until the solids were completely dissolved. The solvent was then removed under vacuum, and the residue suspended in brine (50 mL). The aqueous suspension was extracted with EtOAc (2×50 mL), and the combined organic extracts were dried over MgSO4, filtered and evaporated to yield a clear oil. The oil was dissolved in CHCl3 (1 mL) and subjected to column chromatography (40×350 mm) on silica gel with 10% MeOH/CHCl3. Fractions containing product were pooled and evaporated to yield a pale yellow solid which was recrystallized from 10% MeOH/CHCl3 and hexane to yield 67 mg (75%) of 4.78 as a white crystalline solid: mp 140-141 C; Rf0.5 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.46 (s, 1H), 8.14 (s, 1H), 7.86 (s, 1H), 6.88 (d, 1H), 6.68 (s, 1H), 6.47 (dd, 1H), 5.42 (d, 1H, D2O exch.), 5.23 (s, 1H, D2O exch.), 4.45 (d, 1H), 3.89 (d, 1H), 3.73 (s, 2H), 2.55 (m, 1H), 2.13 (m, 1H). 13C-NMR (125 MHz, DMSO-d6): δ 146.54, 142.25, 132.30, 125.61, 124.39, 124.09, 122.64, 120.75, 114.98, 111.51, 106.91, 104.87, 87.25, 85.04, 69.98, 60.91, 38.97. HRMS (EI) m/z calcd. for C17H14Cl3NO4 400.9988, found 400.9986. Anal calcd for C17H14Cl3NO4.¼H2O: C, 50.15; H, 3.59; N, 3.44. Found: C, 50.17; H, 3.65; N, 3.43.
Reaction SMILES: [Cl-].[CH3:2][Si:3]([C:6]#[C:7][Zn+])([CH3:5])[CH3:4].[N+:9]([C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[C:14](Cl)=[O:15])([O-:11])=[O:10].[Cl-].[NH4+]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N+:9]([C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[C:14](=[O:15])[C:7]#[C:6][Si:3]([CH3:5])([CH3:4])[CH3:2])([O-:11])=[O:10]
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Reactant: C[Si](C)(C)C#C[Zn+]
Agent: [Pd]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C[Si](C)(C)C#CC(=O)c1ccccc1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
The above solution of (trimethylsilyl)ethynyl)zinc(II) chloride (16) in THF was warmed to 0° C., and added to the mixture of 2-nitrobenzoyl chloride (0.94 g) and tetrakis(triphenylphosphine) palladium(0) (176 mg) in tetrahydrofuran at 0° C. under a N2 atmosphere. The reaction mixture was maintained at 0° C. for 30 minutes. Aqueous ammonium chloride solution was added to quench the reaction. It was then extracted 3-times with EtOAc (3×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by preparative TLC to give 300 mg of the desired product (11).
Reaction SMILES: Cl.[N:2]1([CH2:9][C:10]([OH:12])=O)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[NH2:13][C@@H:14]([CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:20][CH:19]=1)=[O:16]>>[N:2]1([CH2:9][C:10]([NH:13][C@@H:14]([CH2:32][O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:15]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)=[O:16])=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1
Reactant: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Reactant: O=C(O)CN1CCCCCC1
Agent: Cl
Product: O=C(CN1CCCCCC1)N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Yield: 52.2 %

Procedure:
Proceeding as in Example 1, but substituting 2-(azepan-1-yl)acetic acid hydrochloride and (S)-2-amino-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide, gave Compound 128, (S)-2-(2-(azepan-1-yl)acetamido)-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide (21.7 mg, 52.2%); Major isomer: 1H-NMR (400 MHz, DMSO-D6): 10.22 (s, 1H), 7.99 (d, 1H), 7.60 (d, 2H), 7.27-7.33 (m, 5H), 7.19-7.23 (m, 2H), 6.99-7.04 (m, 4H), 4.70 (m, 1H), 4.52 (s, 2H), 3.67-3.79 (m, 2H), 3.10 (m, 2H), 2.51-2.63 (m, 4H), 1.55-1.60 (m, 8 h). MS (EI) for C30H34FN3O4. found 520.6 (MH+).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=1.O.[NH2:11][NH2:12]>O1CCOCC1.O>[C:8]([C:4]1[CH:3]=[C:2]([NH:11][NH2:12])[CH:7]=[CH:6][N:5]=1)#[N:9]
Reactant: NN
Reactant: N#Cc1cc(Cl)ccn1
Solvent: O
Solvent: C1COCCO1
Product: N#Cc1cc(NN)ccn1

Procedure:
4-Chloro-2-cyanopyridine (1 g) was dissolved in hydrazine monohydrate (1 ml) and 1,4-dioxane (10 ml), and stirred overnight under reflux. The reaction solution was diluted with water (30 ml) and extracted repeatedly with ethyl acetate. The organic layer was concentrated to obtain the title compound as a crude product, which was used for the next step without further purification.
Reaction SMILES: C([O:3][C:4](=[O:20])[C@@H:5]([O:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([OH:17])=O)=[CH:9][CH:8]=1)C.[CH:21]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O[C@@H](CC1C=CC(O[C@@H](C(=O)NCCC2C=CC(OC3C=CC=CC=3)=CC=2)C)=CC=1)C(O)=O)C>>[CH:21]([N:34]1[CH2:39][CH2:38][N:37]([C:15](=[O:17])[CH2:14][O:13][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][C@H:5]([O:18][CH3:19])[C:4]([OH:3])=[O:20])=[CH:12][CH:11]=2)[CH2:36][CH2:35]1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CCOC(=O)[C@H](Cc1ccc(OCC(=O)O)cc1)OC
Reactant: c1ccc(C(c2ccccc2)N2CCNCC2)cc1
Agent: CCO[C@@H](Cc1ccc(O[C@H](C)C(=O)NCCc2ccc(Oc3ccccc3)cc2)cc1)C(=O)O
Product: CO[C@@H](Cc1ccc(OCC(=O)N2CCN(C(c3ccccc3)c3ccccc3)CC2)cc1)C(=O)O

Procedure:
The title compound was prepared from (2S)-3-(4-carboxymethoxy-phenyl)-2-methoxy-propionic acid ethyl ester (PREPARATION 3, step 2) and 1-benzhydryl-piperazine via the same procedure used for the preparation of (2S,1R)-2-ethoxy-3-(4-{1-[2-(4-phenoxy-phenyl)-ethylcarbamoyl]-ethoxy}-phenyl)-propionic acid (Example 1, step 3) to produce a colorless oil. MS (ES) for C29H32N2O5 [M+H]+: 489.
Reaction SMILES: [CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)=O.Cl.[NH2:12][OH:13].C([O-])(=O)C.[Na+]>CO.CCOCC>[OH:13][N:12]=[CH:1][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1
Reactant: NO
Reactant: N#Cc1ccc(C=O)cc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: CCOCC
Product: N#Cc1ccc(C=NO)cc1
Temperature: 70 °C
Yield: 89 %

Procedure:
The compound was prepared according to Biasotti et al. Bioorg. Med. Chem. 2003, 11, 2247. A suspension of 4-formylbenzonitrile (500 mg, 3.81 mmol, 1.00 eq), hydroxylamine hydrochloride (290 mg, 4.19 mmol, 1.10 eq), and sodium acetate (1.56 g, 19.05 mmol, 5.00 eq) in MeOH (50 mL) was heated at 70° C. for 4 h before concentration to dryness. The residue was then slurried in Et2O, filtered, and concentrated to afford the desired intermediate (496 mg, 3.39 mmol, 89%).
Reaction SMILES: [OH:1][S:2]([OH:5])(=[O:4])=[O:3].[O:6]([C:13]1[N:14]=[C:15]2[C:21]([CH:22]=[O:23])=[CH:20][N:19]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CC(C)=[O:34].OS(O)(=O)=O.[O:41]=[Cr:42](=[O:44])=[O:43]>O.CC(C)=O>[CH3:8][C:7]([CH3:12])=[O:6].[OH:4][S:2]([OH:5])(=[O:3])=[O:1].[O:41]=[Cr:42](=[O:44])=[O:43].[O:6]([C:13]1[N:14]=[C:15]2[C:21]([C:22]([OH:34])=[O:23])=[CH:20][N:19]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: C[Si](C)(C)CCOCn1cc(C=O)c2nc(Oc3ccccc3)cnc21
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: C[Si](C)(C)CCOCn1cc(C(=O)O)c2nc(Oc3ccccc3)cnc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 65 %

Procedure:
A stock solution of Jones reagent (2.67 M) was prepared by carefully adding concentrated H2SO4 (2.3 mL) to CrO3 (2.67 g) then diluting to 10 mL with H2O. To a solution of 2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (2.35 g, 6.37 mmol) in acetone (75 mL) at 0° C. was added Jones reagent (5 mL, 13.4 mmol) dropwise. The reaction mixture was stirred at room temperature for 2 h then quenched with i-PrOH (2 mL), diluted with EtOAc, and filtered over Celite, rinsing with EtOAc. The filtrate was washed with cold water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by SiO2 column chromatography (30-70% EtOAc/hexanes) to provide 1.59 g (65%) of 2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow solid.
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH:8]=[O:9].[CH3:10][O:11][C:12]([C:14]1[C:15]([CH2:20]Cl)=[N:16][CH:17]=[CH:18][CH:19]=1)=[O:13]>CN(C)C=O>[CH3:10][O:11][C:12]([C:14]1[C:15]([CH2:20][N:3]2[CH:7]=[CH:6][CH:5]=[C:4]2[CH:8]=[O:9])=[N:16][CH:17]=[CH:18][CH:19]=1)=[O:13]
Reactant: COC(=O)c1cccnc1CCl
Reactant: O=Cc1ccc[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1cccnc1Cn1cccc1C=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of sodium hydride (5.8 g, 0.12 mol) in dry N,N-dimethyl formamide (25 mL) was added slowly under nitrogen a solution of pyrrole 2-carboxaldehyde (10.5 g, 0.11 mol) in N,N-dimethylformamide (10 mL). The reaction mixture was stirred at room temperature for 30 minutes, then cooled to 5° C. and 2-chloromethyl-pyridine-3-carboxylic acid methyl ester of Step A added slowly while the temperature was being maintained at or below 20° C. After the addition was complete the reaction was stirred at room temperature for 30 minutes. The mixture was evaporated to dryness, and the residue was dissolved in ethyl acetate (250 mL). This solution was washed with water and dried over anhydrous magnesium sulfate. The solvent was then removed in vacuo leaving a dark crystalline solid (23.4 g), which was purified by chromatography on silica gel eluting with a gradient of ethyl acetate/petroleum ether to provide the title compound as a tan crystalline solid (13.75 g), m.p. 91-93° C.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]([C:6]1([NH2:12])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].C(N(CC)CC)C.[Br:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl>[CH3:2][O:3][C:4]([C:6]1([NH:12][S:27]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[Br:20])(=[O:29])=[O:28])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:5]
Reactant: COC(=O)C1(N)CCCCC1
Reactant: O=S(=O)(Cl)c1ccccc1Br
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C1(NS(=O)(=O)c2ccccc2Br)CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 50.8 %

Procedure:
In a 50-mL flask, 1-amino-cyclohexanecarboxylic acid methylester hydrochloride (350 mg, 1.80 mmol) and methylenechloride (20 mL) were charged, and then triethylamine (0.836 mL, 5.99 mmol) was charged, followed by stirring for 30 minutes at room temperature. 2-bromo-benzenesulfonylchloride (383 mg, 1.49 mmol) was added thereto, followed by stirring for 12 hours at room temperature. Then, purified water (10 ml) was added thereto to bring the reaction to an end. The organic layer was separated, and washed with saturated ammonium chloride solution (20 ml). Then, the washed organic layer was separated, and added with magnesium sulfate so as to remove remaining moisture. Then, through filtering and vacuum distillation, the solvent was removed so as to obtain the residue. The mixture was purified with column chromatography (EA/n-Hex=1:5) so as to obtain 1-(2-bromo-benzenesulfonylamino)-cyclohexanecarboxylic acid methylester (285 mg, 51%).
Reaction SMILES: [NH2:1]CCCCCCN.[C:9](O)(=O)[CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15]>>[NH2:1][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15]
Reactant: NCCCCCCN
Reactant: O=C(O)CCCCC(=O)O
Product: NCCCCCC(=O)O

Procedure:
from 5% to 35% by weight of units derived from equimolar quantities of hexamethylene diamine and adipic acid.
Reaction SMILES: ClN1C(=O)CCC1=O.CSC.[C:12]1([CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:19]2[CH2:22][CH2:21][CH:20]2[CH2:23][OH:24])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.CCOCC>[C:12]1([CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:19]2[CH2:22][CH2:21][CH:20]2[CH:23]=[O:24])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: OCC1CCN1C(c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1Cl
Solvent: CCN(CC)CC
Solvent: CSC
Solvent: CCOCC
Product: O=CC1CCN1C(c1ccccc1)c1ccccc1
Reaction time: 0.42 h
Yield: 67.4 %

Procedure:
To a solution of 2.36 g (17.7 mmoles) of N-chlorosuccinimide in 40 ml of dry toluene is added 1.77 ml (24.2 mmoles) of dimethyl sulfide, and the mixture is stirred at the same temperature for 25 minutes and cooled to -25° C. to -30° C. A solution of 3 g (11.8 mmoles) of 1-diphenylmethyl-2-hydroxymethylazetidine in 8 ml of toluene is dropwise added thereto in a period of 20 minutes and the mixture is stirred at the same temperature for 2 hours. A solution of 2.5 ml (11.8 mmoles) of triethylamine in 2 ml of toluene is dropwise added thereto in a period of 15 minutes. The reaction mixture is stirred at -25° C. for 30 minutes, mixed with 120 ml of ether, stirred at room temperature for 5 minutes, washed twice with 50 ml of water, dried over sodium sulfate and evaporated under reduced pressure. The resulting syrupy residue (3.2 g) is dissolved in 50 ml of methylene chloride and extracted four times with 20 (w/w) % aqueous sodium hydrogensulfite solution. The extract is washed with 20 ml of methylene chloride, adjusted to pH 10 with 20% aqueous sodium carbonate solution, and extracted four times with 50 ml of methylene chloride. The extract is washed with water, dried over sodium sulfate and evaporated under reduced pressure. The resulting syrupy residue (2.1 g) is recrystallized from a mixture of n-hexane and ether to yield 2 g of 1-diphenylmethyl-2-formylazetidine in 67% yield.
Reaction SMILES: C[B-:2]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[N+](C)(C)C.C1(Br)C=CC=CC=1.[Mg].B(F)(F)F.CCOCC>C(OCC)C>[C:15]1([B:2]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C[B-](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C[N+](C)(C)C
Agent: FB(F)F
Agent: [Mg]
Solvent: CCOCC
Solvent: Brc1ccccc1
Product: c1ccc(B(c2ccccc2)c2ccccc2)cc1

Procedure:
More specifically, in the case of the tetramethylammonium methyltriphenylborate, phenyl bromide is reacted with metallic magnesium in diethyl ether to prepare a Grignard reagent, the reagent is added dropwise to a solution containing boron trifluoride diethyl etherate dissolved in diethyl ether, the mixed solution is stirred for several hours to obtain triphenylborane, the triphenylborane obtained is added to methyllithium without passing through isolation to form lithium methyltriphenylborate, and tetramethylammonium bromide is added thereto to effect ion exchanging, as a result, tetramethylammonium methyltriphenylborate is obtained.