Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][Si:3][O:4]C.[CH:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:12]3[N:44]=[C:43]4[N:45]=[C:36]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:42]=54)[N:35]=[C:33]4[NH:34][C:26]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:32]=54)=[N:25][C:23]4=[N:24][C:16]([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=54)=[N:15][C:14]=2[NH:13]3)[CH:11]=1.O>C1(=O)OC(C)CO1>[OH:2][Si:3][OH:4].[CH:7]1[CH:6]=[CH:11][C:10]2[C:9](=[C:14]3[N:15]=[C:16]4[N:24]=[C:23]([C:22]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=54)[N:25]=[C:26]4[NH:34][C:33]([C:32]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=54)=[N:35][C:36]4=[N:45][C:43]([C:42]5[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=54)=[N:44][C:12]=2[NH:13]3)[CH:8]=1
Reactant: CO[Si]OC
Agent: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Solvent: O
Solvent: CC1COC(=O)O1
Product: O[Si]O
Temperature: 25 °C

Procedure:
10 g of dimethoxysilicon phthalocyanine synthesized in Synthesis Example 2 was added to 10 g of water and 90 g of propylene carbonate (90% PCN aqueous solution) and reacted at 120° C. for 3 hours. The reaction product was thermally filtrated and washed with DMF and acetone in the order named. After the product was stirred in 50 ml of acetone at room temperature, crystals were separated by filtration and dried to obtain 8.4 g of dihydroxysilicon phthalocyanine. When structural analysis was carried out by mass spectral (negative measurement) and IR (KBr method) methods, the same spectrum as that of Example 1 was obtained. Therefore, it was confirmed that the product was dihydroxysilicon phthalocyanine. According to the X-ray spectrum (FIG. 13), the obtained dihydroxysilicon phthalocyanine is a dihydroxysilicon phthalocyanine having the crystal form of the present invention and a main peak at a 2 θ of 9.20 and other peaks at 12.2, 14.0, 15.3, 19.7, 23.4 and 27.1°, respectively.
Reaction SMILES: F[C:2](F)(F)[C:3]([O:5][C:6]([CH3:10])([CH3:9])[C:7]#[CH:8])=O.[C:13]([C:15]1[CH:20]=CC(O)=[CH:17][CH:16]=1)#[N:14]>O>[CH3:9][C:6]([O:5][C:3]1[CH:17]=[CH:16][C:15]([C:13]#[N:14])=[CH:20][CH:2]=1)([CH3:10])[C:7]#[CH:8]
Reactant: C#CC(C)(C)OC(=O)C(F)(F)F
Reactant: N#Cc1ccc(O)cc1
Solvent: O
Product: C#CC(C)(C)Oc1ccc(C#N)cc1

Procedure:
The 1,1-dimethyl-2-propynyl trifluoroacetate solution, maintained at 0° C., was added to the 4-cyanophenol solution over a 35 minute period while keeping the temperature at ~0 ° C. The resulting mixture was stirred at ~0° C. (ice bath). After stirring for 90 minutes, water (10 mL) was added and the resulting mixture was concentrated at reduced pressure. The residue was partitioned between water (50 mL) and toluene (300 mL). The organic fraction was washed with 1N HCl (3×50 mL), 1N NaOH (2×50 mL), 1N NaHCO3, and brine. After drying (magnesium sulfate), the solvent was removed at reduced pressure to give crude title compound as a yellow oil. Distillation of the crude material (bulb to bulb) afforded the title compound as a colorless, low melting solid (8.93 g).
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].CC1C=C(C)C=C(C)C=1S(O)(=O)=O.[C:20]([O:24][C:25](=[O:38])[NH:26][CH2:27][CH2:28][N:29]1[CH2:36][CH:35]2[O:37][CH:31]([CH2:32][NH:33][CH2:34]2)[CH2:30]1)([CH3:23])([CH3:22])[CH3:21].[O:39]1[CH2:41][C@H:40]1[CH2:42][O:43][C:44]1[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=1>O>[C:48]([C:47]1[CH:50]=[CH:51][C:44]([O:43][CH2:42][C@@H:40]([OH:39])[CH2:41][N:33]2[CH2:32][CH:31]3[O:37][CH:35]([CH2:36][N:29]([CH2:28][CH2:27][NH:26][C:25](=[O:38])[O:24][C:20]([CH3:23])([CH3:21])[CH3:22])[CH2:30]3)[CH2:34]2)=[CH:45][CH:46]=1)#[N:49]
Reactant: N#Cc1ccc(OC[C@@H]2CO2)cc1
Reactant: CC(C)(C)OC(=O)NCCN1CC2CNCC(C1)O2
Agent: Cc1cc(C)c(S(=O)(=O)O)c(C)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC(C)(C)OC(=O)NCCN1CC2CN(C[C@H](O)COc3ccc(C#N)cc3)CC(C1)O2
Temperature: 75 °C
Reaction time: 8 h
Yield: 87 %

Procedure:
Aqueous sodium carbonate solution (1M, 53 mL) was added to a solution of [2-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-ethyl]-carbamic acid tert-butyl ester 2,4,6-trimethylbenzenesulfonic acid salt (50.0 g) in water (100 mL). Solid 4-[(2S)-oxiranylmethoxy]benzonitrile (19.1 g) was added and was rinsed into the reaction flask with water (50 mL). The reaction was heated to 75° C. for 3 hours and then left to stir at ambient temperature overnight. Toluene (350 mL) was added followed by aqueous sodium hydroxide (2M, 90 mL). The mixture was stirred for 5 minutes and then the phases were separated. The aqueous phase was discarded and the toluene phase washed with aqueous citric acid (10% w/v, 180 mL). The toluene phase was discarded. MIBC (240 mL) and aqueous sodium hydroxide (5M, 180 mL) were added to the citric acid phase. After mixing well the phases were separated and the aqueous discarded. The MIBC was washed with aqueous sodium chloride (20% w/v, 50 mL). The MIBC was concentrated under vacuum at <55° C. Solvent was collected (water 13 mL, MIBC 29 mL). The MIBC solution was cooled to ambient temperature and filtered, washing through with MIBC (50 mL). Solvent (152 mL) was distilled under vacuum at <66° C. and then distillation was stopped. IPE (360 mL) was added causing the temperature to fall from 65° C. to 37° C. After stirring for 15 minutes T fell by 2° C. to 35° C. and crystallisation started. The mixture was left to cool to ambient temperature overnight with stirring. The mixture was cooled to 5° C. and the product collected by filtration. The solid was washed on the filter with IPE (150 mL) and sucked dry. Further drying in vacuo at 55° C. gave the title compound as a white solid (41.2 g, 87%).
Reaction SMILES: [CH2:1]=[CH2:2].[C:3]1([CH3:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>>[CH2:1]([C:6]1[CH:7]=[CH:8][C:3]([CH3:9])=[CH:4][CH:5]=1)[CH3:2]
Reactant: C=C
Reactant: Cc1ccccc1
Product: CCc1ccc(C)cc1

Procedure:
Para-ethyltoluene was prepared from toluene and ethylene using the catalyst as obtained in Example 1 under the following reaction conditions:
Reaction SMILES: [CH3:1][NH2:2].F[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12]>CO>[F:10][C:8]1[CH:7]=[CH:6][C:5]([N+:11]([O-:13])=[O:12])=[C:4]([CH:9]=1)[NH:2][CH3:1]
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: CN
Solvent: CO
Product: CNc1cc(F)ccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
An aqueous solution of 40% methyl amine (61 mL, 0.71 mol) was added dropwise to a methanol solution (200 mL) of 2,4-difluoronitrobenzene (46.7 g, 0.29 mol) under ice cooling, and the mixture was stirred for 1 hour under the same temperature. The reaction solution was poured into ice water. Precipitated crystals were collected by filtration, followed by washing with water. The resulting crystals were dried at 50° C., thereby obtaining 47.6 g of a yellow, powdery target compound (yield: 95%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[N:10]=1)[C:5](O)=[O:6].Cl.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:8]=[C:9]([CH3:11])[N:10]=1
Reactant: Cc1cc(C(=O)O)cc(Cl)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1cc(CO)cc(Cl)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.8 %

Procedure:
To a stirred solution of 2-Chloro-6-methyl-isonicotinic acid (2 g, 11.65 mmol) in anhydrous THF (40 ml) cooled in an ice bath, was added 1M borane-methyl sulfide complex (6 ml, 60 mmol). After 1 hr, the mixture was stirred for 48 hr at room temperature. The mixture was cooled in an ice bath and conc. HCl (18 ml) was added and stirred for 30 min. The mixture was then basified by addition of 50% aqueous NaOH (15 ml). The product was extracted with dichloromethane, dried with anhydrous potassium carbonate, filtered, and evaporated in vacuo. The crude product was purified by silica gel column chromatography (eluent, methanol:dichloromethane (5:95)) to afford 1.3 g (71%) of a pale yellow solid; m.p. 112-113° C.; 1H NMR (200 MHz, CDCl3) δ 2.26 (1H, t, J=5.4 Hz), 2.52 (3H, s), 4.70 (2H, d, J=5.4 Hz), 7.15 (1H, s), 7.16 (1H, s); m/z (EI) 157 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH2:4].Cl.N([O-])=O.[Na+].[N-:15]=[N+:16]=[N-].[Na+].[OH-].[Na+]>CC(OC)(C)C.O>[N:4]([C:3]1[C:2]([Cl:1])=[CH:8][CH:7]=[CH:6][C:5]=1[Cl:9])=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1c(Cl)cccc1Cl
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: O
Product: [N-]=[N+]=Nc1c(Cl)cccc1Cl
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 99.1 %

Procedure:
A solution of 2,6-dichloroaniline (100 g, 617 mmol) in MTBE (1 L) is added via addition funnel over 30 minutes to commercial hydrogen chloride (600 mL). The white suspension is stirred 15 minutes and is cooled to 0° C. A solution of sodium nitrite (42.5 g, 617 mmol) in water (150 mL) is added dropwise via addition funnel. After stirring at 0° C. for 30 minutes, a solution of sodium azide (40.1 g, 617 mmol) in water (150 mL) is added. After the addition is completed (45 minutes), the mixture is stirred at 5-10° C. for 30 minutes. The reaction mixture is basified (pH 12) with 50% aq. NaOH, and is stirred for 30 more minutes. The phases are separated and the aqueous layer is extracted three times with MTBE. The combined organic layers are dried over magnesium sulfate and filtered. Toluene (1 L) is added to the organic layer and the solution is concentrated under reduced pressure to a volume of 760 mL to yield the title compound (115 g, 100% conversion, 0.8M solution) as a toluene solution. ES/MS m/e 188 (M+1).
Reaction SMILES: [ClH:1].C(OC([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:16])[CH3:15])=O)C1C=CC=CC=1.[CH:20]1[N:24]([CH2:25][O:26][CH:27]([CH2:30]O)[CH2:28][OH:29])[C:23]2[N:32]=[C:33]([NH2:37])[N:34]=[C:35]([OH:36])[C:22]=2[N:21]=1>[Pd].C(O)(C)C>[CH3:16][CH:14]([C@H:13]([NH2:12])[C:17]([O:19][CH2:30][CH:27]([O:26][CH2:25][N:24]1[C:23]2[NH:32][C:33]([NH2:37])=[N:34][C:35](=[O:36])[C:22]=2[N:21]=[CH:20]1)[CH2:28][OH:29])=[O:18])[CH3:15].[ClH:1]
Reactant: Nc1nc(O)c2ncn(COC(CO)CO)c2n1
Reactant: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: [Pd]
Agent: Cl
Solvent: CC(C)O
Product: CC(C)[C@H](N)C(=O)OCC(CO)OCn1cnc2c(=O)nc(N)[nH]c21
Yield: 77.8 %

Procedure:
Hydrochloric acid (2.08 g) and 10% palladium on carbon (0.88 g, 50% wet) was added to a solution of mono-benzyloxycarbonyl-L-valine ganciclovir (8 g) in 30% aqueous iso-propanol (Iso-propanol:Water::64 mL:28 mL). The reaction mixture was flushed with nitrogen twice and hydrogenated at 35° C. to 40° C. under hydrogen pressure of 0.5-1 Kg/cm2 for about 1 hour. After completion of the reaction, the reaction mass was filtered and washed with 20% aqueous iso-propanol (Iso-propanol:Water::6.4 mL:1.6 mL). Iso-propanol (123.3 mL) was added at about 20° C. to 25° C. in about 1 hour. The reaction mass was cooled to about 10° C. to 15° C. and maintained for about 1 hour, filtered, washed with 10% aqueous iso-propanol solution (10 mL) followed by washing with iso-propanol (10 mL) and dried to obtain valganciclovir hydrochloride (4.8 g).
Reaction SMILES: [ClH:1].C(OC([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:16])[CH3:15])=O)C1C=CC=CC=1.[CH:20]1[N:24]([CH2:25][O:26][CH:27]([CH2:30]O)[CH2:28][OH:29])[C:23]2[N:32]=[C:33]([NH2:37])[N:34]=[C:35]([OH:36])[C:22]=2[N:21]=1.C(O)(C)C>[Pd].CO>[CH3:16][CH:14]([C@H:13]([NH2:12])[C:17]([O:19][CH2:30][CH:27]([O:26][CH2:25][N:24]1[C:23]2[NH:32][C:33]([NH2:37])=[N:34][C:35](=[O:36])[C:22]=2[N:21]=[CH:20]1)[CH2:28][OH:29])=[O:18])[CH3:15].[ClH:1]
Reactant: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: Nc1nc(O)c2ncn(COC(CO)CO)c2n1
Agent: [Pd]
Agent: Cl
Solvent: CC(C)O
Solvent: CO
Product: CC(C)[C@H](N)C(=O)OCC(CO)OCn1cnc2c(=O)nc(N)[nH]c21
Temperature: 2.5 °C
Reaction time: 1 h
Yield: 77.8 %

Procedure:
Hydrochloric acid (2.6 g) and 10% palladium on carbon (1.1 g, 50% wet) were added to a solution of mono-benzyloxycarbonyl-L-valine ganciclovir (10 g) in aqueous methanol (Methanol:Water::50 mL:8 mL) at ambient temperature. The reaction mass was flushed with nitrogen twice and hydrogenated at about 35° C. to 40° C. at hydrogen pressure of about 0.5-1 kg/cm2 for about 1 hour. The reaction mass was filtered and washed with methanol (10 mL). Methanol was distilled out completely under reduced pressure at about 30° C. to 35° C. The residue was dissolved in water (8 mL) and stirred to obtain clear solution. Iso-propanol (56 mL) was added slowly over a period of about 1 hour. The reaction mass was cooled to about 0 to 5° C., maintained for about 1 hour, filtered, washed with 10% aqueous iso-propanol (10 mL) followed by washing with iso-propanol (10 mL) and dried to obtain valganciclovir hydrochloride (6 g).
Reaction SMILES: [Cl-].[NH4+:2].C1(C)C=CC=CC=1.C[Al](C)C.[Cl:14][C:15]1[N:16]=[CH:17][C:18]([C:21]([O:23]C)=O)=[N:19][CH:20]=1.C(=O)([O-])O.[Na+]>C1C=CC=CC=1.O>[Cl:14][C:15]1[N:16]=[CH:17][C:18]([C:21]([NH2:2])=[O:23])=[N:19][CH:20]=1
Reactant: [NH4+]
Reactant: COC(=O)c1cnc(Cl)cn1
Agent: C[Al](C)C
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: O
Solvent: c1ccccc1
Product: NC(=O)c1cnc(Cl)cn1
Temperature: 50 °C
Reaction time: 1 h
Yield: 43 %

Procedure:
Ammonium chloride (558 mg, 10.4 mmol) was suspended in benzene (5 ml) and 2M-trimethylaluminum toluene solution (5.2 ml, 10.4 mmol) was added dropwise at 0° C. After stirring for 1 hr, a solution of methyl 5-chloropyrazine-2-carboxylate (600 mg, 3.48 mmol) in benzene (5 ml) was added. The reaction mixture was heated to 50° C., and stirred overnight. After cooling, the reaction mixture was poured into water, and neutralized with saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=100:0→98:2) to give 5-chloropyrazine-2-carboxamide (236 mg, yield 43%) as a white solid.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].Cl.[N:8]1([C:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[S:16][N:15]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[Cl:23][C:24]1[CH:32]=[C:31]2[C:27]([CH2:28][C:29](=[O:33])[NH:30]2)=[CH:26][C:25]=1[CH2:34][CH2:35]Cl>O>[CH:20]1[CH:21]=[CH:22][C:17]2[S:16][N:15]=[C:14]([N:8]3[CH2:13][CH2:12][N:11]([CH2:35][CH2:34][C:25]4[CH:26]=[C:27]5[CH2:28][C:29](=[O:33])[NH:30][C:31]5=[CH:32][C:24]=4[Cl:23])[CH2:10][CH2:9]3)[C:18]=2[CH:19]=1
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Reactant: O=C1Cc2cc(CCCl)c(Cl)cc2N1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=C1Cc2cc(CCN3CCN(c4nsc5ccccc45)CC3)c(Cl)cc2N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Sodium carbonate (56.3 g) and 500 mL of water were placed into a round bottom flask. Added was 50 g of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride and 50 g of 6-Chloro-5-(2-Chloroethyl)oxindole. The reaction mixture was then refluxed for 15 hours. The reaction completion was monitored by TLC. The reaction mass was cooled to room temperature. The resulting compound was filtered and washed with 50 mL of water. The wet compound and 250 mL of acetone were placed into a flask and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered to give a solid cake, which was washed with 50 mL of acetone. The wet cake and 750 mL of methanol were placed into a flask, which was heated to 50° C., and 14 mL of methane sulfonic acid was added to the solution over 20 minutes. The resulting reaction mass was cooled to room temperature and was subjected to a filtration to give a solid compound, which was washed with methanol. The wet compound and 750 mL of water were placed into a flask, and then pH of the solution was adjusted to pH 9 with caustic lye. The reaction mixture was then stirred at room temperature for 1 hour and filtered. The filtered compound was washed with water and dried at 70° C. to give 65 g of crystalline form Ziprasidone base.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([OH:16])=[O:15])[CH2:9]1)=O)(C)(C)C.[ClH:17]>C(O)(=O)C>[ClH:17].[NH:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([OH:16])=[O:15])[CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](C(=O)O)C1
Agent: Cl
Solvent: CC(=O)O
Product: O=C(O)[C@H]1CCCNC1
Temperature: 15 °C
Reaction time: 4 h
Yield: 99.7 %

Procedure:
(S)-Piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (20 kg, 87.2 mol) was slurried in acetic acid (189 kg) and cooled to 15° C. An excess of hydrogen chloride gas (9.6 kg) was charged and stirred for ˜4 hours to complete deprotection. The slurry was isolated and filter-cake rinsed with acetic acid (2×31.5 kg). The filter cake was then vacuum dried to obtain product (14.4 kg).
Reaction SMILES: Br[C:2]1[S:6][C:5]([N:7]([CH:15]([CH3:17])[CH3:16])[C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:4][CH:3]=1.C([Li])CCC.C(O[B:27]1[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]1)(C)C.[Cl-].[NH4+]>C1COCC1>[C:10]([O:9][C:8](=[O:14])[N:7]([CH:15]([CH3:17])[CH3:16])[C:5]1[S:6][C:2]([B:27]2[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]2)=[CH:3][N:4]=1)([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)N(C(=O)OC(C)(C)C)c1ncc(Br)s1
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)N(C(=O)OC(C)(C)C)c1ncc(B2OC(C)(C)C(C)(C)O2)s1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 48.6 %

Procedure:
A solution of tert-butyl 5-bromothiazol-2-yl(isopropyl)carbamate (Intermediate 43-1, 7.5 g, 23.3 mmol) in THF (50 mL) was treated with n-butyllithium (1.6 M in hexane, 21.8 mL, 34.88 mmol) dropwise at −78° C. The resulting solution was stirred at −78° C. for 10 min, then was treated dropwise with 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.49 g, 34.9 mmol). The mixture was stirred at −78° C. for 2 h, then was warmed to rt and treated with 50% aqueous ammonium chloride (50 mL). The mixture was extracted with EtOAc (100 mL) and the organic layer was washed with water and brine, and dried and concentrated. The residue was slurried in hexane (30 mL) and the precipitate was collected by filtration, washed with hexane (20 mL) and dried to give tert-butyl-isopropyl(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazol-2-yl)carbamate as a yellow solid (4.17 g, 48%). 1H NMR (400 MHz, chloroform-d) δ 7.95 (s, 1H) 5.37 (m, 1H) 1.60 (s, 9H) 1.44 (d, 6.7 Hz, 6H) 1.34 (s, 12H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]1([CH2:15][C:16](Cl)=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)(Cl)Cl.CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:16](=[O:17])[CH2:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: COc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1ccc(C(=O)Cc2ccccc2)cc1
Reaction time: 2 h

Procedure:
To 10.8 g (0.10 mole) methoxybenzene and 13.9 g. (0.09 mole) phenylacetyl chloride in 1.0 1. methylene chloride there are added, by small amounts, 13.3 g. (0.10 mole) aluminium chloride at room temperature and with strong agitation. The reaction mixture is agitated for a further 2 hours and then is poured onto ice and 50 ml. hydrochloric acid are added. After separation of the organic phase, the aqueous solution is shaken out twice with 500 ml. methylene chloride each time, the combined organic phases are washed with water and the solvent is removed in vacuo. The smeary residue is freed of the volatile components by steam distillation and the remaining solid is crystallized from ethanol after filtration and washing with water. Obtained are colorless crystals having a melting point of 75° C.; Rf 0.7 [CHCl3 /CH3OH (9/1)]; yield: 18.3 g. (90%).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][OH:5].[N+:6]([C:9]1[CH:14]=[CH:13][C:12](F)=[CH:11][CH:10]=1)([O-:8])=[O:7].C([O-])([O-])=O.[K+].[K+].O>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].CN(C)C=O>[N+:6]([C:9]1[CH:14]=[CH:13][C:12]([N:2]([CH2:3][CH2:4][OH:5])[CH3:1])=[CH:11][CH:10]=1)([O-:8])=[O:7]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CNCCO
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Solvent: CN(C)C=O
Product: CN(CCO)c1ccc([N+](=O)[O-])cc1
Yield: 74.5 %

Procedure:
5.25 g of N-methylethanolamine, 11.2 g of p-nitrofluorobenzene, 9.7 g of K2CO3 and 2 drops of tricaprylmethylammonium chloride in 70 ml of dimethylformamide were heated at 95° C. for 3 days. The resulting reaction mixture was poured onto 350 ml of water. The precipitated product was filtered off under suction, after which the aqueous phase was extracted with toluene. After drying and evaporating down the toluene solution, the two product fractions were combined and recrystallized from ethanol/water in a volume ratio of 2 1. 10.22 g of 2-[N-(p-nitrophenyl)-N-methylamino]-ethanol having the following physical properties were obtained: melting point: 99°-101° C., IR spectrum (KBr pellet): bands at 3,450, 2,900, 2,850, 1,690, 1,680, 2,900, 1,580, 1,470, 1,450, 1,330, 1,320, 1,110, 1,060 and 825 cm-1 ; 1H nuclear magnetic resonance spectrum (400 MHz, CDCl3, tetramethylsilane as internal standard, chemical shift δ (in ppm): 8.05 (doublet, 2H), 6.64 (doublet, 2H), 3.9 (triplet, 2H), 3.65 (triplet, 2H), 3.15 (singlet, 3H) 2.02 (singlet, 1H).
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]2=[C:7](C(O)=O)[N:8]=[CH:9][N:4]2[CH:3]=1.C1(O)C=CC=CC=1>ClC1C=CC(Cl)=CC=1Cl.CCCCCC>[Br:1][C:2]1[S:6][C:5]2=[CH:7][N:8]=[CH:9][N:4]2[CH:3]=1
Reactant: O=C(O)c1ncn2cc(Br)sc12
Solvent: Clc1ccc(Cl)c(Cl)c1
Solvent: Oc1ccccc1
Solvent: CCCCCC
Product: Brc1cn2cncc2s1
Temperature: 180 °C
Reaction time: 24 h
Yield: 53.4 %

Procedure:
A solution of 2-bromoimidazo[5,1-b]thiazole-7-carboxylic acid (31 mg, 0.12 mmol) and phenol (12 mg, 0.12 mmol) dissolved in 1,2,4-trichlorobenzene (1 ml) was stirred at 180° C. for 24 hr. The reaction solution was allowed to cool to room temperature, was diluted with hexane, and was extracted with 1 M hydrochloric acid (3 ml×3). The aqueous layer was neutralized with a 2 M aqueous solution of sodium hydroxide and was extracted with ethyl acetate (5 ml×3). The organic layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 2-bromoimidazo[5,1-b]thiazole (13 mg, 50%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:12]=[CH:11][CH:10]=[C:6]([C:7](O)=[O:8])[CH:5]=1.[CH3:14][S:15]([NH2:18])(=[O:17])=[O:16].Cl.CN(C)CCCN=C=NCC>CN(C1C=CN=CC=1)C.ClCCl>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:12]=[CH:11][CH:10]=[C:6]([C:7]([NH:18][S:15]([CH3:14])(=[O:17])=[O:16])=[O:8])[CH:5]=1
Reactant: CS(N)(=O)=O
Reactant: COC(=O)c1cccc(C(=O)O)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: COC(=O)c1cccc(C(=O)NS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a mixture of isophthalic acid monomethyl ester (500.0 mg, 2.8 mmol), methanesulfonamide (340 mg, 3.6 mmol) and DMAP (440 mg, 3.6 mmol) in anhydrous dichloromethane (30 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (690 mg, 3.6 mmol). The mixture was allowed to stir for 12 hours at room temperature and then concentrated under reduced pressure. The residue was chromatographed on a Biotage 40M eluting with 2% methanol/98% dichloromethane to provide the titled compound. MS (EST) m/e 259 (M+H)+, 257 (M−H)−; 1H NMR (300 MHz, CD3OD) δ ppm 3.36 (s, 3 H) 3.95 (s, 3 H) 7.64 (t, J=7.80 Hz, 1 H) 8.13 (dd, J=7.80, 1.36 Hz, 1 H) 8.25 (m, 1 H) 8.55 (m, 1 H).