Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][NH2:13])[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20].[C:21](OCC)(OCC)(OCC)[CH3:22]>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[C:21]([CH3:22])=[N:13][N:12]=[C:7]1[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20]
Reactant: CCOC(C)(OCC)OCC
Reactant: NNc1cc(-c2ccccc2F)c2cc(Cl)ccc2n1
Solvent: Cc1ccccc1C
Product: Cc1nnc2cc(-c3ccccc3F)c3cc(Cl)ccc3n12

Procedure:
In the manner given in Example 2, 6-chloro-4-(o-fluorophenyl)-2-hydrazinoquinoline and triethyl orthoacetate are refluxed in xylene to give 7-chloro-1-methyl-5-(o-fluorophenyl)-s-triazolo[4,3-a]quinoline.
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([NH2:11])[CH2:3][CH2:2]1.[Br:12]Br>CC(O)=O>[Br:12][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[O:1][CH2:2][CH2:3][CH:4]2[NH2:11]
Reactant: NC1CCOc2ccccc21
Reactant: BrBr
Solvent: CC(=O)O
Product: NC1CCOc2ccc(Br)cc21
Temperature: 25 °C

Procedure:
A solution of chroman-4-ylamine (Step B) (2.550 g, 17.09 mmol) in AcOH (50 mL) at RT was treated with Br2 (3.01 g, 0.96 mL, 18.8 mmol) drop-wise. The reaction was stirred at RT until HPLC analysis showed complete consumption of starting material. The mixture was diluted with H2O (100 mL) and NaOH was added until the solution became basic. The aqueous layer was extracted with EtOAc until tlc analysis of the aqueous layer showed no evidence of the title compound. The combined organics were dried over MgSO4 and concentrated in vacuo to yield the crude compound, which was purified by flash column chromatography to afford the pure title compound. MS (APCI pos) 229 (M+H).
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18]O.C1(C)C=CC=CC=1>C(OCC)(=O)C>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][CH3:12])=[O:10]
Reactant: COCCOCCO
Reactant: O=C(O)CCCCCCCBr
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COCCOCCOC(=O)CCCCCCCBr
Yield: 78.4 %

Procedure:
8-Bromooctanoic acid (22.3 g), 2-(2-methoxyethoxy)-ethanol (14.08 g) and p-toluenesulphouic acid (0.1 g) were added to toluene (250 ml ) and the resulting soution heated at reflux temperature for 16 hours. Ethyl acetate (500 ml) was then added and the solution washed with aqueous K2CO3 solution and water, dried and evaporated. The residual oil was distilled to give 2-(2-methoxyethoxy)-ethyl 8-bromooctanoate (25.5 g), 77%) as a colourless oil, b.p. 126°-128° C./0.08 mm Hg.
Reaction SMILES: ClC(Cl)(Cl)C[O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:31])[C@@H:14]([NH:16][C:17](=[O:30])[C@@H:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6].C([O-])(=O)C.[NH4+]>O1CCCC1.O.[Zn]>[C:26]([O:25][C:23]([NH:22][C@@H:18]([CH:19]([CH3:21])[CH3:20])[C:17]([NH:16][C@@H:14]([CH3:15])[C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@@H:7]([C:5]([OH:6])=[O:4])[NH:8]1)=[O:31])=[O:30])=[O:24])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)O)N1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Zinc dust (273 mg, 4.18 mmol) was added to a solution of (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (98 mg, 0.19 mmol) in tetrahydrofuran (15 mL). This suspension was treated with a solution of ammonium acetate (220 mg, 2.85 mmol) in water (5 mL). After stirring at room temperature for 3 h, zinc residues were filtered off and the volatiles were removed in vacuo. The residue was partitioned between ethyl acetate and saturated potassium hydrogen sulfate solution and the volatiles were removed in vacuo. The residual acetic acid was removed by azeotroping with toluene (3×10 mL) to give crude (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid which was combined with crude (E)-2,2-dimethyl-4-[2-((R)-1-methylamino-ethyl)-quinolin-7-yl]-but-3-enoic acid methyl ester in anhydrous acetonitrile (10 mL) and N,N-diisopropylethylamine (0.165 mL, 0.95 mmol). This solution was then treated with 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (94 mg, 0.25 mmol). After stirring at room temperature for 16 h, the volatiles were removed in vacuo. The residue was dissolved in ethyl acetate, and subsequently washed with saturated ammonium chloride solution and sodium bicarbonate solution. The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 10 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/acetone 1:0 to 1:1 to afford the title compound (90 mg, 68%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 0.82-1.00 (m, 6H), 1.28-1.40 (m, 3H), 1.50-1.55 (m, 15H), 1.69 (d, J=6.9 Hz, 3H), 1.73-2.12 (m, 5H), 2.76-2.92 (m, 5H), 3.74 (s, 3H), 3.84-4.00 (m, 1H), 4.25-4.45 (m, 1H), 5.22-5.40 (m, 1H), 6.25 (q, J=6.9 Hz, 1H), 6.57-6.74 (m, 2H), 7.35-7.48 (m, 1H), 7.69-7.77 (m, 1H), 7.80-7.88 (m, 1H), 7.90-8.00 (m, 2H), 8.18-8.30 (m, 1H). LCMS (m/z) 695.4 [M+H], Tr=3.00 min.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([NH2:13])[CH:10]=[CH:11][CH:12]=1.[Cl:14][C:15]1[N:16]=[C:17](Cl)[C:18]2[N:23]=[CH:22][S:21][C:19]=2[N:20]=1.CCN(C(C)C)C(C)C>CC(O)C>[Cl:14][C:15]1[N:16]=[C:17]([NH:13][C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([N:3]3[CH2:4][CH2:5][CH2:6][C@@H:2]3[CH3:1])[CH:8]=2)[C:18]2[N:23]=[CH:22][S:21][C:19]=2[N:20]=1
Reactant: C[C@H]1CCCN1c1cccc(N)c1
Reactant: Clc1nc(Cl)c2ncsc2n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: C[C@H]1CCCN1c1cccc(Nc2nc(Cl)nc3scnc23)c1
Yield: 86.6 %

Procedure:
A mixture of (S)-3-(2-methylpyrrolidin-1-yl)benzenamine (0.9 g, 5.34 mmol), 5,7-dichlorothiazolo[5,4-d]pyrimidine (1.1 g, 5.34 mmol), DIEA (1.4 g, 10.68 mmol) in IPA (15 mL) was heated to reflux for 2 hours. Then the reaction mixture was concentrated and residue purified by column chromatography (petroleum ether:ethyl acetate=8:1) to give (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (1.6 g, 91.4%) as yellow solid. LC-MS: 346 [M+H]+, tR=1.82 min.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15](Cl)[CH:14]=2)=[C:11]2[C:6]([N:7]([CH3:23])[C:8](=[O:22])[N:9]([CH3:21])[C:10]2=[O:20])=[CH:5]1.BrC1C=C(C=CC=1)[C:28]#[N:29]>>[NH2:1][CH2:2][CH2:3][N:4]1[C:12]([C:13]2[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=2)[C:28]#[N:29])=[C:11]2[C:6]([N:7]([CH3:23])[C:8](=[O:22])[N:9]([CH3:21])[C:10]2=[O:20])=[CH:5]1
Reactant: Cn1c(=O)c2c(-c3cccc(Cl)c3)n(CCN)cc2n(C)c1=O
Reactant: N#Cc1cccc(Br)c1
Product: Cn1c(=O)c2c(-c3cccc(C#N)c3)n(CCN)cc2n(C)c1=O

Procedure:
The title compound was prepared analogously to Intermediate B by replacing 1-bromo-3-chlorobenzene with 3-bromobenzonitrile.
Reaction SMILES: [C:1]([N:11]1[CH2:34][CH2:33][CH2:32][C@H:12]1[C:13]([NH:15][C:16]1[CH:17]=[C:18]([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[C:19](=[CH:23][CH:24]=1)[C:20]([OH:22])=O)=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.C1(NC(NC2CCCCC2)=O)CCCCC1>C(OCC)(=O)C>[C:1]([N:11]1[CH2:34][CH2:33][CH2:32][C@H:12]1[C:13]([NH:15][C:16]1[CH:24]=[CH:23][C:19]2[C:20](=[O:22])[O:31][C:26]([C:27]([F:30])([F:28])[F:29])=[N:25][C:18]=2[CH:17]=1)=[O:14])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: O=C(O)c1ccc(NC(=O)[C@@H]2CCCN2C(=O)OCc2ccccc2)cc1NC(=O)C(F)(F)F
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C(NC1CCCCC1)NC1CCCCC1
Solvent: CCOC(C)=O
Product: O=C(Nc1ccc2c(=O)oc(C(F)(F)F)nc2c1)[C@@H]1CCCN1C(=O)OCc1ccccc1
Temperature: 0 °C

Procedure:
A solution was prepared by dissolving 100 mg of 4-(N-carbobenzoxy-L-prolyl)amino-N-trifluoroacetyl-anthranilic acid in 1 ml of dry ethyl acetate and cooled to a temperature of 0° C. The solution was mixed with 49 mg of N,N'-dicyclohexylcarbodiimide and the resultant mixture was stirred at a temperature of 4° C. for 18 hours. The resultant deposit consisting of N,N'-dicyclohexylurea and separated from the mixture was removed by filtration.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([SH:23])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25].CS(O[CH2:31][C:32]1[C:37]([F:38])=[CH:36][C:35]([O:39][CH2:40][CH2:41][CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])=[CH:34][C:33]=1[Cl:51])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[Si:44]([O:43][CH2:42][CH2:41][CH2:40][O:39][C:35]1[CH:36]=[C:37]([F:38])[C:32]([CH2:31][S:23][C:14]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[C:3]([O:24][CH3:25])[CH:4]=3)([CH3:10])[CH3:9])=[CH:12][N:13]=2)=[C:33]([Cl:51])[CH:34]=1)([C:47]([CH3:49])([CH3:50])[CH3:48])([CH3:46])[CH3:45]
Reactant: CC(C)(C)[Si](C)(C)OCCCOc1cc(F)c(COS(C)(=O)=O)c(Cl)c1
Reactant: COc1cc(C(C)(C)c2cnc(S)n2-c2ccc(F)cc2)ccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(OCCCO[Si](C)(C)C(C)(C)C)cc3Cl)n2-c2ccc(F)cc2)ccc1F
Reaction time: 2 h
Yield: 71.9 %

Procedure:
To a stirred solution of 5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol (548 mg, 1.52 mmol) and 4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-chloro-6-fluorobenzyl methanesulfonate (681 mg, 1.60 mmol) in CH3CN (5 mL) was added Cs2CO3 (743 mg, 2.28 mmol, 1.5 eq). The reaction mixture was stirred for 2 h, filtered and evaporated in vacuo to give a residue, which was purified by flash column chromatography (EtOAc/Hex=1:4) to afford 2-(4-(3-(tert-Butyldimethylsilyloxy)propoxy)-2-chloro-6-fluorobenzylthio)-5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (756 mg, 72%). 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 1H), 6.85 (dd, J=11.04, 8.48 Hz, 1H), 6.80-6.72 (m, 2H), 6.66 (dd, J=2.37, 1.50 Hz, 1H), 6.56 (dd, J=8.11, 2.19 Hz, 1H), 6.48 (ddd, J=8.41, 4.28, 2.19 Hz, 2H), 6.44 (d, J=2.45 Hz, 1H), 6.39-6.32 (m, 2H), 4.19 (d, J=1.41 Hz, 2H), 3.99 (t, J=6.19 Hz, 2H), 3.83-3.72 (m, 5H), 1.95 (dd, J=12.08, 6.05 Hz, 2H), 1.48 (s, 6H), 0.96-0.84 (m, 10H), 0.03 (t, J=4.73 Hz, 6H).
Reaction SMILES: C[O:2][C:3](=[O:32])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:12]1=[O:31].[OH-].[Na+]>>[O:31]=[C:12]1[N:11]([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:32])=[O:2])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=1
Reactant: COC(=O)CCCCCCCn1c(=O)n(Cc2cccc(C(F)(F)F)c2)c2ccccc21
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)CCCCCCCn1c(=O)n(Cc2cccc(C(F)(F)F)c2)c2ccccc21

Procedure:
The product is produced as described in example 22 from 5.7 g. of 8-[2-oxo-3-(3-trifluoromethylbenzyl)-benzimidazolin-1-yl]-caprylic acid methyl ester and 1.5 g. of NaOH.
Reaction SMILES: [CH2:1]([C:3]1([CH3:22])[CH:8]([CH3:9])[CH:7]([NH:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][C:5]([CH2:20][CH3:21])([CH3:19])[NH:4]1)[CH3:2].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>S1(=O)(=O)CCCC1.C1(C)C=CC=CC=1>[CH2:23]([N:4]1[C:5]([CH2:20][CH3:21])([CH3:19])[CH2:6][CH:7]([NH:10][C:11](=[O:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:8]([CH3:9])[C:3]1([CH2:1][CH3:2])[CH3:22])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CCC1(C)CC(NC(=O)c2ccccc2)C(C)C(C)(CC)N1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O=S1(=O)CCCC1
Product: CCC1(C)CC(NC(=O)c2ccccc2)C(C)C(C)(CC)N1Cc1ccccc1
Temperature: 25 °C

Procedure:
20 g of 2,6-diethyl-2,3,6-trimethyl-4-benzamidopiperidine (compound no. 9), 12.5 g of benzylbromide, 1 g of potassium iodide and 20 g of potassium carbonate are stirred in 200 ml of tetrahydrothiophene dioxide (sulpholane) at 110° C. for 4 days. Thereafter the reaction mixture is diluted with 200 ml of toluene, cooled to room temperature and purified by filtration. The filtrate is washed four times with about 200 ml of water, the toluene phase is dried over sodium sulfate and evaporated under vacuum. Crystallization of the residue from acetic acid ethyl ester yields 1-benzyl-2,6-diethyl-2,3,6-trimethyl-4-benzamidopiperidine (compound no. 48); m.p. 234°-236° C.
Reaction SMILES: C(N(CC)CC)C.[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([OH:22])=O)[CH:18]=3)[CH:13]=[CH:12]2)[CH2:10][CH2:9]1.Cl.[O:26]=[C:27]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39]([C:42]3[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=3)[C:45]([OH:47])=[O:46])[CH:40]=2)[O:35][C:29]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28]1.Cl>CN(C=O)C.O>[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([N:32]4[CH2:33][CH2:34][C:29]5([CH2:28][C:27](=[O:26])[C:41]6[C:36](=[CH:37][CH:38]=[C:39]([C:42]7[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=7)[C:45]([OH:47])=[O:46])[CH:40]=6)[O:35]5)[CH2:30][CH2:31]4)=[O:22])[CH:18]=3)[CH:13]=[CH:12]2)[CH2:9][CH2:10]1
Reactant: COc1cc(C(=O)O)cc2c1ccn2C1CC1
Reactant: O=C(O)c1cccc(-c2ccc3c(c2)C(=O)CC2(CCNCC2)O3)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(C(=O)N2CCC3(CC2)CC(=O)c2cc(-c4cccc(C(=O)O)c4)ccc2O3)cc2c1ccn2C1CC1
Temperature: 70 °C
Reaction time: 7 h

Procedure:
N,N′-carbonyldiimidazole (130 mg) and triethylamine (0.446 mL) were added to a solution of 1-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acid (185 mg) in DMF (4 mL), and stirred at 70° C. for 7 hours. To the reaction mixture was added 3-(4-oxo-spiro[chroman-2,4′-piperidin]-6-yl)benzoic acid hydrochloride (374 mg), which was further stirred at that temperature for 16 hours. 1 N hydrochloric acid and water were added to the reaction mixture, and the formed solid was collected by filtration. The resulting solid was recrystallized from methanol, and purified through silica gel column chromatography (chloroform/methanol) to obtain 3-{1′-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid. This was suspended in water (5 mL), and aqueous 1 N sodium hydroxide solution (0.762 mL) was added thereto and stirred at room temperature for 30 minutes. The solution was purified through ODS reversed-phase column chromatography (water/methanol) to obtain the intended compound. 1H-NMR (400 MHz, DMSO-d6) δ: 8.11-8.09 (1H, m), 7.96-7.93 (1H, m), 7.90 (1H, dd, J=8.5, 2.4 Hz), 7.83-7.79 (1H, m), 7.56-7.50 (1H, m), 7.32 (1H, dd, J=7.6, 7.6 Hz), 7.29 (1H, d, J=3.2 Hz), 7.23 (1H, s), 7.20 (1H, d, J=8.5 Hz), 6.59 (1H, s), 6.41-6.39 (1H, m), 4.45-4.11 (1H, br m), 3.86 (3H, s), 3.86-3.55 (1H, br m), 3.52-3.22 (3H, m), 2.93 (2H, s), 2.17-1.64 (4H, br m), 1.11-1.00 (2H, m), 0.96-0.88 (2H, m); MS [M+Na]+=573.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:12])=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5](O)=[O:6]>C1COCC1>[Br:1][C:2]1[C:3]([CH3:12])=[C:4]([CH2:5][OH:6])[CH:8]=[C:9]([CH3:11])[CH:10]=1
Reactant: Cc1cc(Br)c(C)c(C(=O)O)c1
Solvent: C1CCOC1
Product: Cc1cc(Br)c(C)c(CO)c1
Temperature: 25 °C

Procedure:
To a solution of 3-bromo-2,5-dimethylbenzoic acid (3.5 g, 15 mmol) in anhydrous THF was added borane THF complex (1.0 M, 25 mL, 25 mmol) at 0, then the reaction was warmed to ambient temperature overnight. The reaction was quenched with MeOH and concentrated to afford (3-bromo-2,5-dimethylphenyl)methanol.
Reaction SMILES: OS(O)(=O)=O.N([O-])=O.[Na+].N[C:11]1[C:12]([C:21]([OH:23])=[O:22])=[CH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2.O.[ClH:25]>CC(O)=O.C(Cl)Cl.Cl[Cu]>[Cl:25][C:11]1[C:12]([C:21]([OH:23])=[O:22])=[CH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2
Reactant: Nc1cc2ccccc2cc1C(=O)O
Reactant: Cl
Agent: Cl[Cu]
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: O=C(O)c1cc2ccccc2cc1Cl
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a flask containing 35 mL of concentrated H2SO4 is added 3.31 g NaNO2 (47.9 mmol) slowly over 15 minutes. The mixture is stirred an additional 15 minutes before being cooled to room temperature in a cold water bath. A solution of 8.14 g 3-amino-2-naphthoic acid (43.5 mmol) in 65 mL HOAc is added slowly dropwise, keeping the reaction temperature below 40° C. The mixture is stirred for 30 minutes and then poured carefully into an ice-cold solution of 10.14 g CuCl (102.2 mmol) in 65 mL of concentrated HCl. The mixture is heated to 80° C. and stirred for 30 minutes before adding 200 mL of H2O. After stirring an additional 15 minutes, the mixture is filtered and washed with H2O to give a gray solid. The solid is dissolved in 500 mL of CH2Cl2 and the solution is washed 2 times with 100 mL saturated aqueous brine and dried over Na2SO4. Evaporation of the solvents gives a solid that is dried in vacuo to give 3-chloro-2-naphthoic acid as a brown solid.
Reaction SMILES: [NH2:1][CH:2]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=1[O:19][CH3:20])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9]C)=O.[C:21]1([C:27]2[CH:28]=[N:29][CH:30]=[C:31]([CH:34]=2)[CH:32]=O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH3:20][O:19][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=1[CH:2]1[N:1]([CH2:32][C:31]2[CH:30]=[N:29][CH:28]=[C:27]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:34]=2)[C:7](=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=Cc1cncc(-c2ccccc2)c1
Reactant: COC(=O)CCCCC(N)c1c(OC)cccc1OC
Product: COc1cccc(OC)c1C1CCCCC(=O)N1Cc1cncc(-c2ccccc2)c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 6-amino-6-(2,6-dimethoxyphenyl)hexanoate with 5-phenylnicotinaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions I): tR=1.26 min.; [M+H]+: 417.20 g/mol.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([NH2:19])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][C:21]=1[O:30][CH2:31][CH2:32][CH2:33][CH2:34]Cl>CS(C)=O.O>[CH2:7]([NH:19][CH2:34][CH2:33][CH2:32][CH2:31][O:30][C:21]1[CH:22]=[CH:23][C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:20]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCN
Reactant: ClCCCCOc1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCCCCCCCCCNCCCCOc1ccc2ccccc2c1
Temperature: 150 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and n-dodecylamine (0.48 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 4-(2-naphthyloxy)-1-chlorobutane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 150° C. for 8 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(n-dodecyl)-(4-(naphthalen-2-yloxy)-butyl)amine, solid. m.p. 129° C., (yield 0.78 gm, 95.5%).
Reaction SMILES: CC1N=C(N2CCN(C3C=CC=CC=3)C2=O)SC=1C(OCC)=O.[F:24][CH:25]([F:51])[O:26][C:27]1[CH:50]=[CH:49][C:30]([CH2:31][N:32]2[CH2:36][CH2:35][N:34]([C:37]3[S:38][C:39]([C:43]([O:45]CC)=[O:44])=[C:40]([CH3:42])[N:41]=3)[C:33]2=[O:48])=[CH:29][CH:28]=1>>[F:51][CH:25]([F:24])[O:26][C:27]1[CH:50]=[CH:49][C:30]([CH2:31][N:32]2[CH2:36][CH2:35][N:34]([C:37]3[S:38][C:39]([C:43]([OH:45])=[O:44])=[C:40]([CH3:42])[N:41]=3)[C:33]2=[O:48])=[CH:29][CH:28]=1
Reactant: CCOC(=O)c1sc(N2CCN(Cc3ccc(OC(F)F)cc3)C2=O)nc1C
Agent: CCOC(=O)c1sc(N2CCN(c3ccccc3)C2=O)nc1C
Product: Cc1nc(N2CCN(Cc3ccc(OC(F)F)cc3)C2=O)sc1C(=O)O
Yield: 88 %

Procedure:
Following the procedure as described in Example 6, making variations as required to replace ethyl 4-methyl-2-(2-oxo-3-phenylimidazolidin-1-yl)thiazole-5-carboxylate with ethyl 2-(3-(4-(difluoromethoxy)benzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate, the title compound was obtained in 88% yield: 1H NMR (300 MHz, DMSO-d6) δ 7.43-6.94 (m, 5H), 4.39 (s, 2H), 3.97 (t, J=8.1 Hz, 2H), 3.42 (t, J=8.1 Hz, 2H), 2.46 (s, 3H); MS (ES+) m/z 384.2 (M+1).
Reaction SMILES: [O-2:1].[Mg+2:2].[P:3]([O-:7])([OH:6])([OH:5])=[O:4].[NH4+:8]>O>[OH2:4].[OH2:1].[OH2:4].[OH2:4].[OH2:4].[OH2:4].[P:3]([O-:7])([O-:6])([O-:5])=[O:4].[NH4+:8].[Mg+2:2]
Reactant: O=P([O-])(O)O
Reactant: [O-2]
Agent: [Mg+2]
Agent: [NH4+]
Solvent: O
Product: O=P([O-])([O-])[O-]

Procedure:
U.S. Pat. No. 4,428,906 discloses a pressure-transmitting medium prepared from a mixture of borosilicate glass and a refractory powder. The refractory powder consists of magnesium oxide, ammonium dihydrogen phosphate and silica powder in the form of quartz and cristobalite. The borosilicate glass and refractory powders are mixed with water to form a slurry that is cast into the shape of a die. The refractory powder and water react at ambient temperatures to form magnesium ammonium phosphate hexahydrate which acts as a cement to bind the glass and silica powders. The phosphate decomposes to an amorphous phase upon heating to about 250° Centigrade (° C.) during drying. Further heating of the die to about 1100° C. during preheating results in conversion of the amorphous phase to magnesium pyrophosphate or, if excess magnesium oxide is present, magnesium orthophosphate.
Reaction SMILES: N[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].N([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[C-:24]#[N:25].[K+]>Cl.O.[O-]S([O-])(=O)=O.[Cu+2]>[C:24]([C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6])#[N:25]
Reactant: Nc1cc(C(=O)O)cc([N+](=O)[O-])c1
Reactant: [C-]#N
Agent: [Cu+2]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: O
Product: N#Cc1cc(C(=O)O)cc([N+](=O)[O-])c1
Yield: 93.8 %

Procedure:
3-Amino-5-nitrobenzoic acid (3.64 g, 20 mM) was dissolved in concentrated hydrochloric acid (20 ml), diluted with water (75 ml), cooled to 0°, and added over 30 minutes to a solution of NaNO2 (1.38 g, 20 mM) in water (10 ml). The pH was adjusted to 6.2 with saturated Na2CO3 solution. A mixture of CuSO4. 5H2O (10 g, 42 mM) in water (40 ml) and KCN (10 g, 154 mM) in water (20 ml) was heated to 65°, the solution of diazonium salt added over 15 minutes, and the mixture refluxed for 40 minutes. After cooling, and acidifying with 2M hydrochloric acid, the organics were extracted into ethyl acetate (2×200 ml). The combined extracts were washed with aqueous NaH2PO4, water, brine, and dried over Na2SO4. Evaporation gave 3-cyano-5-nitrobenzoic acid (3.6 g, 94%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1.[CH3:22][N:23]([CH3:31])[CH2:24][CH2:25][C:26](=O)[C:27]([OH:29])=[O:28]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:26]([C:27]([OH:29])=[O:28])[CH2:25][CH2:24][N:23]([CH3:31])[CH3:22])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1
Reactant: NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Reactant: CN(C)CCC(=O)C(=O)O
Product: CN(C)CCC(=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1)C(=O)O

Procedure:
In the manner given in Example 13, 7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine can be stirred with 4-(dimethylamino)-2-oxobutanoic acid at room temperature to give 7-chloro-2-[[1-carboxy-3-(dimethylamino)propylidene]hydrazino]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.