Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[C:8]1([C@H:18]([N:20]([CH2:28][C@@H:29]2[C@@H:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:32][NH:31][CH2:30]2)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.Cl>C1COCC1>[C:23]([O:22][C:21]([N:20]([CH2:28][C@@H:29]1[C@@H:33]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:32][N:31]([C:4](=[O:5])[CH2:3][CH2:2][C:1]([OH:6])=[O:7])[CH2:30]1)[C@@H:18]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1)[CH3:19])=[O:27])([CH3:24])([CH3:25])[CH3:26]
Reactant: C[C@H](c1cccc2ccccc12)N(C[C@H]1CNC[C@@H]1c1ccccc1)C(=O)OC(C)(C)C
Reactant: O=C1CCC(=O)O1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@H](c1cccc2ccccc12)N(C[C@H]1CN(C(=O)CCC(=O)O)C[C@@H]1c1ccccc1)C(=O)OC(C)(C)C
Reaction time: 8 h

Procedure:
Succinic anhydride was added to a mixture of 1.0 g of tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[(3R,4S)-4-phenylpyrrolidin-3-yl]methyl}carbamate, 235 mg of triethylamine and 15 ml of THF at room temperature and stirred overnight. The reaction solution was mixed with 1 M hydrochloric acid to quench the reaction and extracted with chloroform. The organic layer was dried with anhydrous sodium sulfate and concentrated under a reduced pressure to obtain 1.72 g of crude 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-4-oxobutanoic acid (compound A) as a colorless amorphous substance. A 1.0 g portion of the thus obtained crude product was purified by a silica gel column chromatography (chloroform-methanol) to obtain 525 mg of 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-4-oxobutanoic acid as a colorless amorphous substance.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=1[NH2:17].C(N(C(C)C)C(C)C)C.[F:27][C:28]([F:46])([F:45])[C:29]1[CH:30]=[C:31]([C:39]([CH3:44])([CH3:43])[C:40](Cl)=[O:41])[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1>C(Cl)Cl>[F:27][C:28]([F:45])([F:46])[C:29]1[CH:30]=[C:31]([C:39]([CH3:43])([CH3:44])[C:40]([NH:17][C:9]2[CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[CH:12]=[CH:13][C:8]=2[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])=[O:41])[CH:32]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:34]=1
Reactant: Cc1ccccc1-c1ccc([N+](=O)[O-])cc1N
Reactant: CC(C)(C(=O)Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccccc1-c1ccc([N+](=O)[O-])cc1NC(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 2 h
Yield: 89 %

Procedure:
A solution of 925 mg (4.05 mmol) 2′-methyl-4-nitro-biphenyl-2-ylamine and 1.03 ml (6.08 mmol) N-ethyldiisopropylamine in 9 ml CH2Cl2 was cooled in an ice bath and a solution of 1.42 g (4.46 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride in 1 ml CH2Cl2 was added dropwise. The reaction mixture was kept at room temperature for 2 hrs. After addition of CH2Cl2, the organic layer washed with 1 N NaOH solution and 1 N HCl solution, dried (MgSO4) and evaporated to give 1.84 g (89%) 2-(3,5-bis-trifluoromethyl-phenyl)-N-(2′-methyl-4-nitro-biphenyl-2-yl)-isobutyramide as yellow crystals, MS (ISP): 511.3 (M+H)+.
Reaction SMILES: [CH3:1][C@@H:2]([NH:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12.Cl.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=1>C1(C)C=CC=CC=1>[C:3]1([CH:2]([N:13]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:45])([F:46])[F:47])[CH:39]=2)[CH2:14][CH2:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[CH3:1])[C:8]2[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=1
Reactant: FC(F)(F)c1cccc(CCCBr)c1
Reactant: C[C@@H](NCCCc1cccc(C(F)(F)F)c1)c1cccc2ccccc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CC(c1cccc2ccccc12)N(CCCc1cccc(C(F)(F)F)c1)CCCc1cccc(C(F)(F)F)c1
Temperature: 27.5 °C

Procedure:
To a stirred solution of Cinacalcet hydrochloride (1, 10 g, 0.028 mol) in toluene (150 mL) was added potassium carbonate (7.74 g, 0.056 mol) followed by 1-(3-bromopropyl)-3-(trifluoromethyl)benzene (5, 14.95 g, 0.056 mol) under stirring at 25-30° C. The reaction mass was heated and stirred at 110-111° C. for 48 h. Upon completion of the reaction (by TLC), the reaction mass was cooled and quenched with water (100 mL). The organic layer was separated, washed with water (100 mL), and concentrated under reduced pressure to obtain a thick oil. The crude oil was then purified by column chromatography on silica gel (70 mm×60 cm column) by eluting with chloroform to afford the title compound as a thick transparent oil. Yield: 10.50 g (69.03%); HPLC purity: 91.22%; IR (NaCl) cm−1: 3441, 3049, 2940, 2861, 1596, 1492, 1449, 1331, 900, 702, 661; MS: m/z=544.0 [M+H]+; 1H NMR (400 MHz, CDCl3): δ=1.35-1.37 (d, 3H), 1.57-1.63 (m, 4H), 2.42-2.46 (t, 4H), 2.52-2.55 (t, 4H), 4.60-4.62 (m, 1H), 7.23-7.25 (d, J=8.0 Hz, 1H), 7.32 (s, 2H), 7.37-7.41 (t, 3H), 7.47-7.51 (m, 6H), 7.76-7.78 (d, J=8.0 Hz, 1H), 7.87-7.89 (dd, 1H), 8.42-8.44 (d, J=8.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): δ=15.46 (CH3), 29.38 (CH2), 32.99 (CH2), 50.03 (CH2), 56.90 (CH), 122.68, 122.72, 122.76, 123.37, 124.78, 124.83, 124.86, 124.91, 125.58, 125.68, 125.72 (CF3), 128.88, 129.28, 129.33, 129.40, 129.49, 129.58, 129.60, 129.91, 132.06, 132.63, 134.04, 140.62, 144.01.
Reaction SMILES: [Na].[O:2]=[C:3]([CH:25]([CH3:27])[CH3:26])[CH2:4][C:5]([NH:7][C@@H:8]1[C:23](=[O:24])[N:10]2[C:11]([C:20]([OH:22])=[O:21])=[C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[CH2:13][S:14][C@H:9]12)=[O:6].[N:28]([O-])=[O:29].[Na+].Cl>C(OCC)(=O)C.O.C(O)(=O)C>[OH:29][N:28]=[C:4]([C:3](=[O:2])[CH:25]([CH3:27])[CH3:26])[C:5]([NH:7][C@@H:8]1[C:23](=[O:24])[N:10]2[C:11]([C:20]([OH:22])=[O:21])=[C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[CH2:13][S:14][C@H:9]12)=[O:6]
Reactant: O=N[O-]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)CC(=O)C(C)C)[C@H]2SC1
Agent: Cl
Agent: [Na+]
Agent: [Na]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)C(=NO)C(=O)C(C)C)[C@H]2SC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 6.1 g. of sodium salt of 7β-(3-oxo-4-methylvaleramido)-3-acetoxymethylceph-3-em-4-carboxylic acid in 60 ml. of glacial acetic acid, are dropped 2.1 g. of sodium nitrite dissolved in 20 ml. of water. After stirring for 2 hours at ambient temperature, there are added 200 ml. of ethyl acetate and 100 ml. of hydrochloric acid 0.1N. The phases are separated and the organic phase is washed with 50 ml. of water, made anhydrous, decolourised over charcoal and concentrated to small volume. The precipitated solid is filtered off to give 1.4 g of 7β-(2-hydroxyimino-3-oxo-4-methylvaleramido)-3-acetoxymethylceph-3-em-4-carboxylic acid melting at 156° C. (with decomposition); [α]D =+76.9° C. (c=2 in tetrahydrofuran/water 1:1).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:2]1.[C:21]1(=O)[CH2:24][CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH:21]1([N:1]2[CH2:4][CH:3]([CH2:5][O:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]4([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[CH:11][CH:12]=3)[CH2:2]2)[CH2:24][CH2:23][CH2:22]1
Reactant: N#CC1(c2ccc(OCC3CNC3)cc2)CCOCC1
Reactant: O=C1CCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: N#CC1(c2ccc(OCC3CN(C4CCC4)C3)cc2)CCOCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.4 %

Procedure:
4-[4-(azetidin-3-ylmethoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile (0.29, 0.73 mmol) was dissolved in THF (2 mL). Cyclobutanone (0.06 mL, 0.80 mmol) and acetic acid (0.042 mL, 0.73 mmol) were added. The mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.311 g, 1.47 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with 10% aqueous sodium carbonate (5 mL) then extracted with DCM (2×50 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to provide a clear oil. This was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 95:5:0.5) to provide the title compound (0.194 g, 81%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.60-1.70 (m, 2H), 1.70-1.80 (m, 2H), 1.80-1.90 (m, 2H), 1.95-2.00 (m, 2H), 2.0-2.15 (m, 2H), 2.9 (m, 1H), 3.1 (t, 2H), 3.16 (m, 1H), 3.4 (t, 2H), 3.9 (m, 2H), 4.10 (m, 4H), 6.90 (d, 2H), 7.40 (d, 2H). HRMS ESI+ m/z 327.2059 [MH]+.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:43]([N:46]1[CH2:51][CH2:50][CH:49]([NH:52][S:53]([CH2:56][CH2:57][NH2:58])(=[O:55])=[O:54])[CH2:48][CH2:47]1)([CH3:45])[CH3:44]>CN(C=O)C>[ClH:1].[CH:43]([N:46]1[CH2:51][CH2:50][CH:49]([NH:52][S:53]([CH2:56][CH2:57][NH:58][C:7]([C:5]2[S:6][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:9])(=[O:54])=[O:55])[CH2:48][CH2:47]1)([CH3:45])[CH3:44]
Reactant: O=C(O)c1ccc(Cl)s1
Reactant: CC(C)N1CCC(NS(=O)(=O)CCN)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)N1CCC(NS(=O)(=O)CCNC(=O)c2ccc(Cl)s2)CC1
Product: Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1.87 g (1.75 equiv.) 5-chloro-thiophene-2-carboxylic acid in 50 ml DMF were added 4.39 g (1.75 equiv.) HATU and 3.35 ml (3 equiv.) DIPEA. The resulting mixture was stirred for 30 min at room temperature. Subsequently a solution of 1.64 g (6.58 mmol) 2-amino-ethanesulfonic acid (1-isopropyl-piperidin-4-yl)-amide and 1.11 ml (1 equiv.) DIPEA in 20 ml DMF was added. The resulting mixture was stirred at room temperature overnight and concentrated under reduced pressure. The resulting residue was taken up in ethyl acetate and filtered. The filtrate was washed with a saturated NaHCO3-solution. Then, the product was extracted into the aqueous phase by treatment with a 0.1 N HCl-solution. Separation of the aqueous phase, then adjusting the pH to ≈9 by treatment with a saturated NaHCO3-solution and subsequent re-extraction with ethyl acetate brought the product back in the organic phase. Concentration under reduced pressure afforded crude 5-chloro-thiophene-2-carboxylic acid [2-(1-isopropyl-piperidin-4-ylsulfamoyl)-ethyl]-amide. Final purification was achieved by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA). Lyophilisation and transformation into its hydrochloride gave the title compound as a colorless, amorphous solid. Yield: 1.76 g MS (ES+): m/e=394, chloro pattern.
Reaction SMILES: [C:1]([C:4]1[NH:5][CH:6]=[NH+:7][C:8]=1[O-:9])(=[O:3])[NH2:2].C(N(CC)CC)C.[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1>CN(C)C=O>[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([O:9][C:8]2[N:7]=[CH:6][NH:5][C:4]=2[C:1](=[O:3])[NH2:2])=[O:23])=[CH:20][CH:19]=1
Reactant: NC(=O)c1[nH]c[nH+]c1[O-]
Reactant: O=C(Cl)c1ccc(Cl)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: NC(=O)c1[nH]cnc1OC(=O)c1ccc(Cl)cc1
Reaction time: 4 h

Procedure:
To a suspension of 508 mg of 4-carbamoylimidazolium-5-olate and 486 mg of triethylamine in 6 ml of anhydrous dimethylformamide was added 770 mg of p-chlorobenzoyl chloride in 3 ml of anhydrous dimethylformamide at a temperature below 5° C. The mixture was stirred under ice cooling for 4 hours. The insoluble crystals were filtered off, then the filtrate were concentrated to a residue under reduced pressure, and the resulting residue was dissolved in chloroform. The chloroform solution was washed with water, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 5-carbamoyl-1H-imidazol-4-yl p-chlorobenzoate. The crude solid was washed with ethyl acetate to give 340 mg of pure product, m.p. 220° C. (charred).
Reaction SMILES: Cl.[CH2:2]([S:4][C:5]1[N:6]([C:10]2[CH:15]=[CH:14][C:13](C)=[CH:12][CH:11]=2)[CH:7]=[CH:8][N:9]=1)[CH3:3].Br.C(O)(=[O:20])C>>[CH2:2]([S:4][C:5]1[N:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[OH:20])[CH:7]=[CH:8][N:9]=1)[CH3:3]
Reactant: CCSc1nccn1-c1ccc(C)cc1
Reactant: CC(=O)O
Agent: Br
Agent: Cl
Product: CCSc1nccn1-c1ccccc1O

Procedure:
A mixture of 14 parts of 2-(ethylthio)-1-(4-methylphenyl)-1H-imidazole monohydrochloride and 113 parts of hydrobromic acid solution 48% in glacial acetic acid is stirred and refluxed for 3 hours. The reaction mixture is evaporated and the residue is dissolved in water. The solution is neutralized with sodium hydrogen carbonate. The precipitated product is filtered off and crystallized from 2-propanol, yielding 8.3 parts (72.5%) of 4-[2-(ethylthio-1H-imidazol-1-yl]phenol; mp. 165.2° C.
Reaction SMILES: C([N:3]([CH2:14][CH3:15])[C:4](=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](C)[C:6]=1[CH3:12])C.[OH:16][CH:17]1[CH2:21][CH2:20][N:19]([CH2:22]CC#N)[CH2:18]1>>[OH:16][CH:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:15][C:14]2[NH:3][C:4](=[O:13])[C:5]3[C:6]([CH:12]=2)=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH2:18]1
Reactant: CCN(CC)C(=O)c1cccc(C)c1C
Reactant: N#CCCN1CCC(O)C1
Product: O=c1[nH]c(CCN2CCC(O)C2)cc2ccccc12
Yield: 13.5 %

Procedure:
By the reaction in the same manner as in Example 1a, using N,N-diethyl-2,3-dimethylbenzamide (4.347 g) and 3-(3-hydroxypyrrolidin-1-yl)propionitrile (1.6 g), 3-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-2H-isoquinolin-1-one (397.6 mg) was obtained.
Reaction SMILES: [C:1]1(=O)[O:7][C:5](=[O:6])[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]2[CH2:2]1.C(=O)([O-])[O-].[NH4+:17].[NH4+]>>[C:1]1(=[O:7])[NH:17][C:5](=[O:6])[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]2[CH2:2]1
Reactant: O=C1Cc2ccccc2C(=O)O1
Reactant: [NH4+]
Agent: O=C([O-])[O-]
Product: O=C1Cc2ccccc2C(=O)N1
Temperature: 280 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
Homophthalic anhydride (1.62 g, 10 mmol) and ammonium carbonate (1.61 g, 10 mmol) are ground in a mortar and then slowly heated to fusion at about 280° C. After 2 h, the reaction mixture is allowed to cool. The product is practically pure and needs no further treatment. Thus homophthalimide is obtained in 95% yield (153 mg).
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]([C:7]1[CH:8]=[C:9]([CH:18]=[C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:20]=1[OH:21])[O:10][CH2:11][C:12]1[S:16][C:15](=[S:17])[NH:14][N:13]=1)([CH3:6])[CH3:5].I[CH3:27]>CO>[CH3:23][C:22]([C:19]1[CH:18]=[C:9]([O:10][CH2:11][C:12]2[S:16][C:15]([S:17][CH3:27])=[N:14][N:13]=2)[CH:8]=[C:7]([C:4]([CH3:3])([CH3:5])[CH3:6])[C:20]=1[OH:21])([CH3:25])[CH3:24]
Reactant: CI
Reactant: CC(C)(C)c1cc(OCc2n[nH]c(=S)s2)cc(C(C)(C)C)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CSc1nnc(COc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)s1
Reaction time: 0.5 h

Procedure:
A solution of 1N sodium hydroxide (1.05 mL, 1.05 mmol) is added over 5 minutes to a solution of 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenoxy]-methyl]-1,3,4-thiadiazole-2(3H)-thione (0.37 g, 1.05 mmol) and iodomethane (0.26 mL, 4.20 mmol) in methanol (10 mL). The reaction is stirred for 30 minutes, then the pink precipitate is filtered and washed with methanol/water. A second crop is collected, and the combined precipitate is (71%) of pink platelets which are 2,6-bis(1,1-dimethylethyl)-4-[(5-methylthio-1,3,4-thiadiazol-2-yl)methoxy]phenol; mp 128.0°-129.5° C.
Reaction SMILES: CCCCN1C(=O)N(CCCC)C(=O)C(=C/C=C/C=C2/N(CCCS([O-])(=O)=O)C3C(O/2)=CC=CC=3)C1=O.[Na+].[CH2:39]([N:41]1[C:45](=[O:46])[C:44](=[C:47](Cl)[CH:48]=[C:49]2[N:53]([CH2:54][CH3:55])[C:52]3[CH:56]=[CH:57][CH:58]=[CH:59][C:51]=3[S:50]2)[S:43][C:42]1=[S:61])[CH3:40].C(#N)C.[I-].[Na+]>C(N(CC)CC)C>[CH2:39]([N:41]1[C:45](=[O:46])[C:44](=[C:47]=[C:48]=[C:49]2[N:53]([CH2:54][CH3:55])[C:52]3[CH:56]=[CH:57][CH:58]=[CH:59][C:51]=3[S:50]2)[S:43][C:42]1=[S:61])[CH3:40]
Reactant: CCN1C(=O)C(=C(Cl)C=C2Sc3ccccc3N2CC)SC1=S
Agent: CCCCN1C(=O)C(=C/C=C/C=C2\Oc3ccccc3N2CCCS(=O)(=O)[O-])C(=O)N(CCCC)C1=O
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCN1C(=O)C(=C=C=C2Sc3ccccc3N2CC)SC1=S
Reaction time: 0.02 h

Procedure:
A mixture of the merocyanine dye of Example 9 (1 g), acetonitrile (100 ml), sodium iodide (5 g) and triethylamine (7 ml) are heated at reflux with stirring for 1 minute and chilled immediately. The dye is collected and washed sequentially with acetonitrile, water, acetonitrile and ether. After recrystallization from acetonitrile, the yield of purified dye is 0.57 g (63%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22].O>C1COCC1>[CH3:20][S:21]([O:12][CH:10]1[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)(=[O:23])=[O:22]
Reactant: CC(C)(C)OC(=O)N1CC(O)C1
Reactant: CS(=O)(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)C1
Reaction time: 1.5 h

Procedure:
Tert-Butyl-3-hydroxyazetidine-1-carboxylate (0.20 g, 1.2 mmol, Aldrich) in THF (10 mL) at 0° C. was treated with triethylamine (0.32 mL, 2.3 mmol) and methanesulfonyl chloride (0.11 mL, 1.4 mmol, Aldrich). After 1.5 hours, water was added, and the aqueous mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated to afford crude tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate, which was used in further step without purification.
Reaction SMILES: C([Mg]Br)C=C.[CH2:6]([B:9]([CH2:13][CH:14]=[CH2:15])[CH2:10][CH:11]=[CH2:12])[CH:7]=[CH2:8].[CH2:16]([O:19][CH3:20])[C:17]#[CH:18].C=CC>C(OCC)C.CO>[B:9]12[CH2:13][CH:14]3[CH2:15][CH:11]([CH2:12][CH:7]([CH2:8]3)[CH2:6]1)[CH2:10]2.[CH2:18]1[CH2:20][O:19][CH2:16][CH2:17]1
Reactant: C#CCOC
Reactant: C=CCB(CC=C)CC=C
Agent: C=CC[Mg]Br
Solvent: C=CC
Solvent: CCOCC
Solvent: CO
Product: C1B2CC3CC1CC(C2)C3
Product: C1CCOC1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 52 %

Procedure:
Under Ar atmosphere and vigorous stirring, to 100 ml (1.0M) of allylmagnesium bromide in diethyl ether was added dropwise 4.8 g of borontrifloride diethyl ether. After refluxing for 30 min, the mixture was permitted to stand over night. The solution layer was transferred to another flask under Ar. The diethyl ether was removed by distillation at 60° C. under normal pressure. The triallyl borane was distilled from the mixture under reduced pressure to yield 2.7 g (60%). To a 100 ml flask preheated to 130° C. was added 2.7 g of triallyl borane. After stirring for 5 min was added 1.4 g of methyl propargyl ether. The mixture was stirred for 1 hour then cooled down to room temperature. To the mixture was added 0.7 ml of methanol and stirred for 15 min after the propene gas evacuated completely. To the remaining oil was added 20 ml (1.0 M) of borane THF complex in THF solution. The mixture was refluxed at 80° C. for 2 hours. The THF was then removed under vacuum at room temperature. The pure 1-boraadamantane THF complex was obtained from the white solid residue via sublimation under vacuum in 2.0 g (yield: 52%). The spectra data were as follows: 1H-NMR (25° C. in CDCl3) δ 3.4 ppm (t, 4H, THF CH2-O), δ 2.7 ppm (m, 3H, CH), δ 1.9 ppm (t, 4H, THF CH2), δ 1.1 ppm (m, CH2). 11B-NMR (25° C. in CDCl3) δ 12.58 ppm (s); 13C-NMR (25° C. in CDCl3) δ 24.1 ppm (s, THF CH2), δ 30.4 ppm (b, CH2-B), δ 34.9 ppm (s, CH), δ 40.8 ppm (s, CH2), δ 68.2 ppm (s, THF CH2—O).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH2:9][OH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:17][S:18](Cl)(=[O:20])=[O:19].C(N(CC)CC)C>O1CCCC1.O>[CH3:17][S:18]([O:10][CH2:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)(=[O:20])=[O:19]
Reactant: CS(=O)(=O)Cl
Reactant: OCCC(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 78.6 %

Procedure:
To a mixed solution of 3,3-diphenyl-1-propanol (24.0 g, 113 mmol) and methanesulfonyl chloride (13.7 g, 120 mmol) in tetrahydrofuran (200 mL) was added triethylamine (17.0 mL, 120 mmol) gradually at 0° C. and the mixture was stirred at room temperature for 10 minutes. This reaction mixture was diluted with water (200 mL) and extracted with 2 portions of ethyl acetate. The combined organic solution was washed with saturated aqueous sodium chloride solution, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was crystallized from diisopropyl ether to provide 25.8 g of the title compound. Yield 79%.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])(C)(C)C.[C:19]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:23][C:22](C(Cl)=O)=[CH:21][CH:20]=1.O[N:35]=[C:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH2:37]>>[CH3:15][O:14][N:13]=[C:11]1[CH2:10][C@@H:9]([C:16]2[O:18][N:37]=[C:36]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:35]=2)[N:8]([C:6]([C:31]2[CH:30]=[CH:29][C:28]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:33][CH:32]=2)=[O:7])[CH2:12]1
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Reactant: CON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Reactant: NC(=NO)c1ccccc1
Product: CON=C1C[C@@H](c2nc(-c3ccccc3)no2)N(C(=O)c2ccc(-c3ccccc3)cc2)C1

Procedure:
Following the general method as outlined in Example 59, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidine-carboxylic acid (Intermediate 2), [1,1′-biphenyl]-4-carbonyl chloride, and N′-hydroxybenzenecarboximidamide, the title compound was obtained in 82% purity by TPLC. MS(ESI+): m/z=439.2.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Ca+2].[I:16]I>CO>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][C:3]=1[I:16]
Reactant: II
Reactant: Nc1ccc(CCO)cc1
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CO
Product: Nc1ccc(CCO)cc1I
Yield: 36.8 %

Procedure:
To a mixture of 4-aminophenethyl alcohol (20 g, 145.8 mmol) and calcium carbonate (18.2 g, 145.8 mmol) in methanol (200 mL) was added iodine (37 g, 182.3 mmol) in portions. The mixture was heated at reflux overnight and then concentrated in vacuo to give a dark brown residue, which was partitioned between ethyl acetate and saturated sodium bisulfite solution. The organic phase was washed with water and brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to give 14.1 g (37%) of desired product as a light brown syrup. MS(APCI+): m/z 264.1 (MH+). The compound was taken to Step B without further purification.
Reaction SMILES: FC1C=CC(C[N:7]2C(=O)N(C3SC(C(O)=O)=C(C)N=3)C=N2)=CC=1.[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][C:46]([F:49])([F:48])[F:47])=[CH:41][CH:40]=3)[C:34]2=[O:50])[S:28][C:29]=1[C:30]([OH:32])=O>>[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][C:46]([F:48])([F:47])[F:49])=[CH:41][CH:40]=3)[C:34]2=[O:50])[S:28][C:29]=1[C:30]([NH2:7])=[O:32]
Reactant: Cc1nc(N2CCN(Cc3ccc(OC(F)(F)F)cc3)C2=O)sc1C(=O)O
Reactant: Cc1nc(-n2cnn(Cc3ccc(F)cc3)c2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(Cc3ccc(OC(F)(F)F)cc3)C2=O)sc1C(N)=O

Procedure:
Following the procedure as described in Example 1, making variations as required to replace 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-thiazole-5-carboxylic acid with 4-methyl-2-(2-oxo-3-(4-(trifluoromethoxy)benzyl)-imidazolidin-1-yl)thiazole-5-carboxylic acid, the title compound was obtained as a colorless solid: mp 185-187° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.42 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.2 Hz, 2H), 7.29 (br, 2H), 4.44 (s, 2H), 4.01 (t, J=7.3 Hz, 2H), 3.48 (t, J=7.3 Hz, 2H), 2.46 (s, 3H); MS (ES+) m/z 400.7 (M+1).