Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][O:5][C:3](=[O:4])[CH:2]=1.[CH2:11](O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.C1COCC1.CN(C)C1C=CN=CC=1>[O:4]=[C:3]1[CH:2]=[CH:1][C:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[CH:6][O:5]1
Reactant: O=C(O)c1ccc(=O)oc1
Reactant: OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)c1ccc(=O)oc1
Temperature: 23 °C
Reaction time: 0.25 h

Procedure:
A solution of coumalic acid (1.2 g, 8.57 mmol) in DCM (20 mL) and THF (20 mL) was treated with 4-dimethylaminopyridine (0.105 g, 0.857 mmol). The reaction was stirred under nitrogen at 23° C. After 15 min, benzyl alcohol (0.886 mL, 8.57 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.642 g, 8.57 mmol) were added, and the stirring was continued. After 5 h, the solution was diluted with DCM (200 mL) and the mixture was washed with water (150 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 5-25% EtOAc/hexane), affording the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.32 (s, 1H), 7.80 (dd, J=9.78, 2.15 Hz, 1H), 7.33-7.48 (m, 5H), 6.33 (d, J=9.78 Hz, 1H), 5.31 (s, 2H). MS (ESI, positive ion) m/z: 231.1 (M+H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:10][CH:9]2[O:24][CH2:25][C:26]2[CH:27]=[CH:28][C:29]3[O:34][CH2:33][C:32](=[O:35])[N:31]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[C:30]=3[CH:41]=2)=[CH:4][CH:3]=1.[O:42]([CH2:49][C@@H:50]1[CH2:52][O:51]1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.[F-].[Cs+]>>[OH:51][C@H:50]([CH2:49][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:52][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:15])[CH2:10][CH:9]2[O:24][CH2:25][C:26]2[CH:27]=[CH:28][C:29]3[O:34][CH2:33][C:32](=[O:35])[N:31]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[C:30]=3[CH:41]=2)=[CH:4][CH:3]=1
Reactant: c1ccc(OC[C@@H]2CO2)cc1
Reactant: COCCCN1C(=O)COc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(O)cc3)cc21
Agent: [Cs+]
Agent: [F-]
Product: COCCCN1C(=O)COc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(OC[C@H](O)COc4ccccc4)cc3)cc21
Temperature: 130 °C
Reaction time: 3 h

Procedure:
The mixture of 0.280 g of benzyl 4-(4-hydroxyphenyl)-3-[4-(3-methoxypropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate, 0.152 g of 2(S)-phenoxymethyloxirane and 0.0015 g of caesium fluoride is stirred at 130° C. over 3 hours. The reaction mixture is cooled and the title compound is obtained as a colourless oil by means of flash chromatography (SiO2 60F). Rf=0.13 (1:1 EtOAc-heptane); Rt=5.14.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C@H:8]([NH:16]C(=O)OC(C)(C)C)[C:9](=[O:15])[N:10]2[CH2:14][CH2:13][S:12][CH2:11]2)[CH2:4][CH2:3]1.[CH:24]1[C:29]([S:30](Cl)(=[O:32])=[O:31])=[CH:28][CH:27]=[C:26]([I:34])[CH:25]=1.N1C=CC=CC=1>C(Cl)Cl>[NH2:16][C@@H:8]([CH:5]1[CH2:4][CH2:3][CH:2]([NH:1][S:30]([C:29]2[CH:24]=[CH:25][C:26]([I:34])=[CH:27][CH:28]=2)(=[O:32])=[O:31])[CH2:7][CH2:6]1)[C:9](=[O:15])[N:10]1[CH2:14][CH2:13][S:12][CH2:11]1
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)N1CCSC1)[C@H]1CC[C@H](N)CC1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: N[C@H](C(=O)N1CCSC1)C1CCC(NS(=O)(=O)c2ccc(I)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 72 %

Procedure:
To a solution of 50 mg (0.139 mmol) of tert-butyl trans-(1S)-1-(4-aminocyclohexyl)-2-oxo-2-(1,3-thiazolidin-3-yl)ethyl-carbamate in 1 mL of methylene chloride was added 53 mg (0.175 mmol) of pipsyl chloride, and 0.022 mL (0.27 mmol) of pyridine, and the reaction was stirred at ambient temperature for 16 h. The solvent was removed in vacuo and the product purified by preparative thin layer chromatography (TLC) (silica gel, 5:95 methanol:methylene chloride) afforded 51 mg of the title compound as is Boc carbamate. Deprotection was effected by treatment with 2 mL of a 1:1 mixture of trifluoroacetic acid:methylene chloride at ambient temperature for 2 h, followed by concentration in vacuo and removal of the excess trifluoroacetic acid by azeotropic distillation with methylene chloride. Purification by preparative TLC (silica gel, 9:1:90 methanol:concentrated ammonium hydroxide:methylene chloride) afforded 37 mg of the title compound. 1H NMR (400 MHz, CD3OD) δ 7.94 (d, 2H, J=8 Hz), 7.58 (d, 2H, J=8 Hz), 4.64–4.62 (m, 0.45H), 4.58–4.52 (m, 1H), 4.47–4.43 (m, 0.55H), 3.91–3.64 (m, 2H), 3.41 (d, 0.45H, J=7 Hz), 3.37 (d, 0.55H, J=7 Hz), 3.07 (t, 1.1H, J=6 Hz), 3.02 (t, 0.9H, J=6 Hz), 3.00–2.92 (m, 1H), 1.84–1.72 (m, 3H), 1.59–1.52 (m, 1H), 1.48–1.38 (m, 1H), 1.23–1.10 (m, 3H), 1.09–0.97 (m, 1H).
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH2:21][NH:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[C:44]([O:48][CH2:49][CH3:50])(=[O:47])[CH:45]=[CH2:46].[O-]CC.[Na+]>C(O)C>[CH2:26]([O:25][CH2:24][CH2:23][N:22]([CH2:21][CH2:20][O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:46][CH2:45][C:44]([O:48][CH2:49][CH3:50])=[O:47])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CCCCCCCC/C=C\CCCCCCCCOCCNCCOCCCCCCCC/C=C\CCCCCCCC
Reactant: C=CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCCCCCC/C=C\CCCCCCCCOCCN(CCOCCCCCCCC/C=C\CCCCCCCC)CCC(=O)OCC
Reaction time: 8 h
Yield: 85.6 %

Procedure:
Compound 67 (400 mg, 0.660 mmol) obtained in Example 67 was dissolved in ethanol (8 mL), and stirred overnight under heat and reflux after adding ethyl acrylate (3.59 mL, 33.0 mmol) and sodium ethoxide (22.5 mg, 0.330 mmol). After cooling the reaction solution, the solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 98/2) to give ethyl 3-(bis(2-((Z)-octadec-9-enyloxy)ethyl)amino)propanoate (399 mg, 85.6%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[CH3:21][C:22]1[N:23]=[C:24]([NH2:28])[S:25][C:26]=1[CH3:27]>>[Cl:20][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:28][C:24]2[S:25][C:26]([CH3:27])=[C:22]([CH3:21])[N:23]=2)=[O:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: Cc1nc(N)sc1C
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: Cc1nc(NC(=O)c2cc([N+](=O)[O-])c(Sc3c(Cl)cncc3Cl)s2)sc1C

Procedure:
Prepared according to the procedure described for example 70 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxylic acid (200 mg, 0.57 mmol) and 4,5-dimethyl-thiazol-2-amine (87 mg, 0.68 mmol). The title compound was obtained as a yellow solid (8 mg, 3% yield). 1H NMR (400 MHz, d6-DMSO) δ: 12.85 (1H, m), 9.01 (2H, m), 2.08 (6H, m). MS m/z: 459.03, 461.02 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH2:15][C:16](O)=[O:17])[C:12]2[CH:19]=[CH:20][CH:21]=[CH:22][C:11]=2[S:10]3)=[CH:4][CH:3]=1.[CH2:23]([NH2:26])[CH2:24][CH3:25]>O1CCCC1>[CH3:1][C:2]1[S:6][C:5]([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH2:15][C:16]([NH:26][CH2:23][CH2:24][CH3:25])=[O:17])[C:12]2[CH:19]=[CH:20][CH:21]=[CH:22][C:11]=2[S:10]3)=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2nc3sc4ccccc4n3c2CC(=O)O)s1
Reactant: CCCN
Solvent: C1CCOC1
Product: CCCNC(=O)Cc1c(-c2ccc(C)s2)nc2sc3ccccc3n12
Temperature: 25 °C
Reaction time: 4 h
Yield: 59.5 %

Procedure:
1.6 g (0.005 mole) of 2-(5-methylthien-2-yl)imidazo[2,1-b]-benzothiazole-3-acetic acid are treated, at room temperature, with 0.85 g (0.005 mole) of N,N'-carbonyldiimidazole in 30 ml of anhydrous tetrahydrofuran for 3 h 30 min. A solution composed of 3 g (0.05 mole) of propylamine in 10 ml of anhydrous tetrahydrofuran is added and the mixture is stirred for 4 h at room temperature. The solvent is evaporated under reduced pressure, the compound is collected by filtration, it is washed with water up to neutral pH, then with ethanol and finally with ethyl ether and it is purified by recrystallization from methanol. 1.1 g of a light yellow solid are obtained. Melting point: 204°-206° C.
Reaction SMILES: [CH3:1][Mg]Br.[O:4]1[CH2:13][C@H:5]1[C:6]([O:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:7].[Cl-].[NH4+]>C(OCC)C.O1CCCC1.[Cu]I>[OH:4][C@@H:5]([CH2:13][CH3:1])[C:6]([O:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:7]
Reactant: CCCCOC(=O)[C@@H]1CO1
Reactant: C[Mg]Br
Agent: [Cu]I
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCCCOC(=O)[C@@H](O)CC
Yield: 99 %

Procedure:
Under argon, copper(I) iodide (594 mg) was suspended in anhydrous diethyl ether (20.0 mL). A solution of methylmagnesium bromide in anhydrous tetrahydrofuran (60.2 mL, M) was added dropwise to the suspension at −15° C. or lower, and the mixture was allowed to react at the same temperature for 20 minutes. After completion of reaction, a solution (8.0 mL) of n-butyl(S)-(−)-2,3-epoxypropionate (3.0 g, 97.3% ee) (product of Osaka Organic Chemical Industry Co., Ltd.) in anhydrous diethyl ether was added dropwise to the reaction mixture at −78° C., and the resultant mixture was allowed to react for 15 minutes at the same temperature. After completion of reaction, an aqueous saturated ammonium chloride solution (50.0 mL) was added to the reaction mixture, followed by filtration by means of a Celite. The filtrate was extracted twice with diethyl ether (50 mL×2), and the organic layer was washed with saturated brine (40 mL). The washed organic layer was dried over sodium sulfate anhydrate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography including elution with methylene chloride/diethyl ether=5/1, to thereby yield 3.37 g of colorless oil (yield 99.0%). Since the compound was also able to be purified through distillation under reduced pressure, another aliquot of the residue obtained through the same procedure was distillated under reduced pressure, to thereby yield 2.73 g of colorless oil (yield 81.8%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:10]2[CH:14]=[C:13]([C:15]([OH:17])=O)[N:12]=[CH:11]2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.[CH3:19][NH:20][CH3:21].C(NC(C)C)(C)C.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[CH3:19][N:20]([CH3:21])[C:15]([C:13]1[N:12]=[CH:11][N:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH:14]=1)=[O:17]
Reactant: CNC
Reactant: O=C(O)c1cn(-c2cccc([N+](=O)[O-])c2)cn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CC(C)NC(C)C
Solvent: CN(C)C=O
Product: CN(C)C(=O)c1cn(-c2cccc([N+](=O)[O-])c2)cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 28.8 %

Procedure:
1-(3-Nitro-phenyl)-1H-imidazole-4-carboxylic acid 2 (0.1 g, 0.4 mmol) was dissolved in DMF (5 mL) and dimethyl amine hydrochloride (33 mg, 0.4 mmol), diisopropyl amine (366 uL, 2.1 mmol), 1-hydroxy-7-azabenzotriazole (HOAt, 68 mg; 0.5 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, hydrochloride (EDC HCl, 96 mg, 0.5 mmol) were added. The mixture was stirred at room temperature for 16 h. The solvent was evaporated and the residue was extracted with hot ethyl acetate. The solvent was evaporated and crystallization from MeOH afforded 30 mg (29%) pure product as white needles. HRMS (ESI+): m/z=260.2518 [M+H]
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[Cl:18][C:19]1[CH:20]=[CH:21][C:22](F)=[C:23]([CH:26]=1)[C:24]#[N:25].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.C(OCC)(=O)C>[C:13]([O:12][C:11](=[O:17])[NH:10][CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([O:1][C:22]2[CH:21]=[CH:20][C:19]([Cl:18])=[CH:26][C:23]=2[C:24]#[N:25])[CH:3]=1)[CH3:9])([CH3:16])([CH3:15])[CH3:14]
Reactant: N#Cc1cc(Cl)ccc1F
Reactant: CC(NC(=O)OC(C)(C)C)c1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(NC(=O)OC(C)(C)C)c1cccc(Oc2ccc(Cl)cc2C#N)c1
Temperature: 100 °C
Yield: 97.5 %

Procedure:
tert-Butyl [1-(3-hydroxyphenyl)ethyl]carbamate (0.025 g, 0.11 mmol) was dissolved in acetonitrile (1.0 mL) with 5-chloro-2-fluorobenzonitrile (Aldrich, Cat. #548693) (0.034 g, 0.22 mmol) and cesium carbonate (0.073 g, 0.22 mmol) in a sealed tube. The reaction was heated to 100° C. for 2 h. and was complete. The reaction was taken up in ethyl acetate, filtered and concentrated under reduced pressure to give crude tert-butyl{1-[3-(4-chloro-2-cyanophenoxy)phenyl]ethyl}carbamate (0.040 g) as a clear oil. Analytical LCMS (M+H-Boc)+: m/z=272.9.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N+:17]([O-])=O)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>C(OCC)(=O)C.CO.[Pd]>[NH2:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:9]=[CH:10]2
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc2c(ccn2Cc2ccccc2)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: Nc1ccc2c(ccn2Cc2ccccc2)c1
Temperature: 25 °C
Yield: 9 %

Procedure:
A solution of 1-benzyl-5-nitroindole (0.51 g, 0.02 mol) in a mixture of ethyl acetate (25 ml) and methanol (25 ml) was carefully added to 10% palladium on charcoal (45 mg). The resulting suspension was stirred at room temperature under an atmosphere of hydrogen. When the reaction was complete (indicated by tlc or calculated uptake of hydrogen) the suspension was filtered through a pad of Harbolite™, and the filtrate evaporated to dryness to give 5-amino-1-benzylindole (0.40 g, 91%) as an off-white solid; m.p. 66-68° C.; δH [2H6]-DMSO 7.30-7.12 (6H, m, 2-H, 2″-H, 3″-H, 4″-H, 5″-H, 6″-H), 7.08 (1H, d, J 8, 7-H), 6.70 (1H, s, 4-H), 6.49 (1H, d, J 8, 6-H), 6.18 (1H, s, 3-H), 5.28 (2H, s, CH2), 4.38 (2H, br s, NH2).
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]1[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=1)[CH:19]=[C:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[N:29]1[CH:34]=[CH:33][CH:32]=[C:31]([NH:35][C:36](=O)[O:37]C2C=CC=CC=2)[CH:30]=1>>[CH2:8]([O:15][C:16]1[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=1)[CH:19]=[C:20]1[CH2:25][CH2:24][N:23]([C:36]([NH:35][C:31]2[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=2)=[O:37])[CH2:22][CH2:21]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: O=C(Nc1cccnc1)Oc1ccccc1
Reactant: C(=C1CCNCC1)c1cccc(OCc2ccccc2)c1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cccnc1)N1CCC(=Cc2cccc(OCc3ccccc3)c2)CC1
Yield: 94.8 %

Procedure:
Following the procedure in Example 1, Step 6, 4-(3-benzyloxy-benzylidene)-piperidine trifluoroacetate (550 mg, 1.4 mmol, from Step 3) and phenyl pyridin-3-ylcarbamate (331 mg, 1.55 mmol) were used to provide the title compound (530 mg). MS (APCI 10 V) AP+ 400.2; 1H NMR (400 MHz, CD3OD) δ ppm 2.40-2.46 (m, 2H) 2.46-2.52 (m, 2H) 3.48-3.54 (m, 2H) 3.60-3.66 (m, 2H) 5.08 (s, 2H) 6.40 (s, 1H) 6.76-6.89 (m, 3H) 7.22 (t, J=8.09 Hz, 1H) 7.26-7.46 (m, 5H) 7.86-7.95 (m, J=8.36, 2.48, 1.45, 0.89 Hz, 1H) 8.16 (dd, J=4.81, 1.40 Hz, 1H) 8.58 (d, J=2.53 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([I:18])=[C:4]([CH2:13][O:14][C:15](=[O:17])[CH3:16])[C:5]([I:12])=[C:6]([C:10]=1[I:11])[C:7](Cl)=[O:8].[CH2:19]([CH2:21][NH2:22])[OH:20]>>[NH2:1][C:2]1[C:3]([I:18])=[C:4]([CH2:13][O:14][C:15](=[O:17])[CH3:16])[C:5]([I:12])=[C:6]([C:10]=1[I:11])[C:7]([NH:22][CH2:21][CH2:19][OH:20])=[O:8]
Reactant: NCCO
Reactant: CC(=O)OCc1c(I)c(N)c(I)c(C(=O)Cl)c1I
Product: CC(=O)OCc1c(I)c(N)c(I)c(C(=O)NCCO)c1I

Procedure:
5-Amino-3-acetoxymethyl-2,4,6-triiodobenzoyl chloride was reacted with ethanolamine according to the general procedure in Example 24g. The yield of isolated product was 98%.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[O:6][C@@:5]([CH3:10])([CH:7]=[N:8][OH:9])[CH2:4][O:3]1.[Cl:12]N1C(=O)CCC1=O>CN(C=O)C.O>[OH:9][N:8]=[C:7]([Cl:12])[C@@:5]1([CH3:10])[CH2:4][O:3][C:2]([CH3:11])([CH3:1])[O:6]1
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC1(C)OC[C@](C)(C=NO)O1
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OC[C@](C)(C(Cl)=NO)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.7 %

Procedure:
(S)-2,2,4-Trimethyl-1,3-dioxolane-4-carbaldehyde oxime (5.7 g, 36 mmol) was dissolved in DMF (120 mL) and 1-chloropyrrolidine-2,5-dione (4.8 g, 36 mmol) was added. The reaction was stirred at ambient temperature overnight, and then poured in water (600 mL) with stirring. After 15 minutes the cloudy suspension was extracted with EtOAc, washed with water and brine, dried over sodium sulfate, filtered and concentrated to afford (R)-N-hydroxy-2,2,4-trimethyl-1,3-dioxolane-4-carbimidoyl chloride (6.4 g, 33 mmol, 92% yield).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[CH2:7][CH2:6][N:5]=1.[CH2:18]=[O:19]>CO>[OH:1][CH2:2][CH:3]([CH2:18][OH:19])[C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[CH2:7][CH2:6][N:5]=1
Reactant: COc1cc2c(cc1OC)C(CCO)=NCC2
Reactant: C=O
Solvent: CO
Product: COc1cc2c(cc1OC)C(C(CO)CO)=NCC2

Procedure:
To 0.01 mole of 1-(β-hydroxyethyl)-6,7-dimethoxy-3,4-dihydroisoquinoline 2 ml of a 37% aqueous formaldehyde solution are added, and the mixture is boiled in 30 ml of methanol for 2 hours. After evaporation the obtained oily residue is triturated with ether. Crystallization of the obtained product from a mixture of acetone and ether affords the desired compound, which has the same spectral characteristics as the product of Example 1. Melting point: 129° to 131 C.°
Reaction SMILES: Cl[CH2:2][C@@H:3]([OH:22])[C@@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]([F:13])[CH:7]=1.[OH-].[K+].O>C(O)C>[F:13][C:8]1[CH:7]=[C:6]([CH2:5][C@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:3]2[CH2:2][O:22]2)[CH:11]=[C:10]([F:12])[CH:9]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1cc(F)cc(F)c1)[C@H](O)CCl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H](Cc1cc(F)cc(F)c1)[C@H]1CO1
Reaction time: 1 h

Procedure:
To a 250 mL 3-neck round bottom flask equipped with magnetic stir bar, nitrogen inlet and thermocouple, is added tert-butyl (1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV, EXAMPLE 3, 3.5 g, 0.010 moles, 1 equivalent) followed by absolute ethanol (60 mL) and cooled to 0°. To this mixture is added potassium hydroxide (0.73 g, 0.013 moles, 1.25 equivalents) dissolved in absolute ethanol (10 mL) over 1 hr and the resulting suspension is warmed to 15-20° and stirred for 1 hr. At this time, water (100 mL) is added and the reaction contents are cooled to −5° and stirred for 30 min. The solids are collected by filtration and washed with cold water (2×25 mL) then dried under reduced pressure at 45° to give the title compound, mp=133°; NMR (DMSO-d6) δ 7.03, 3.61, 2.68-2.98 and 1.33; CMR (DMSO-d6) δ 163.72, 161.29, 155.55, 143.35, 112.65, 101.80, 78.17, 53.42, 52.71, 44.90, 36.98 and 28.36.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH2:3][CH2:4][CH3:5].[CH2:8](Br)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>O1CCCC1>[CH3:5][CH2:4][CH2:3][CH2:2][CH2:1][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCC/C=C\CCCCCCCCBr
Reactant: CCCCC[Mg]Br
Solvent: C1CCOC1
Product: CCCCCCCC/C=C\CCCCCCCCCCCCC
Yield: 99 %

Procedure:
To a stirred solution of 1.15 moles of amylmagnesium bromide in 335 ml. anhydrous tetrahydrofuran at -8° is added 0.028 moles of lithium chlorocyanocuprate in tetrahydrofuran, prepared in Example 1 above. Dropwise addition of 1.00 moles of Z-9-octadecenyl bromide is carried out with cooling to maintain the temperature at from about -6° to +5°. The reaction mixture is maintained at -5° to +5° for 1 hour. Magnesium bromide is precipitated by the addition of hexane and a minor amount of water. The slurry of granular solid is filtered and washed with hexane. Evaporation of solvent from the filtrate gives a clear amber oil of Z-9-tricosene in 99% yield.
Reaction SMILES: [NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH:12](=O)[CH3:13].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[CH2:12]([N:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[CH:2]1)[CH3:13]
Reactant: CC=O
Reactant: C1=CNc2ccccc2C=C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CCN1C=CC=Cc2ccccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 79.4 %

Procedure:
To a solution of the secondary benzazepine (0.98 g, 3.9 mmol) from step E above in dichloromethane (50 mL) were added acetaldehyde (0.44 mL, 7.7 mmol), sodium triacetoxyborohydride (1.8 g, 8.3 mmol), acetic acid (0.2 mL), and 3 Å molecular sieves (1.0 g). The reaction solution was stirred at room temperature for 24 h and then it was diluted with dichloromethane, washed with aqueous 1 N sodium carbonate, dried over sodium sulfate and concentrated in vacuo. The crude product obtained was purified by flash column chromatography (dichloromethane to 95:4.5:0.5 dichloromethane/methanol/concentrated ammonium hydroxide) to give the desired N-ethyl benzazepine (0.53 g, 48%) as a yellow oil: 1H NMR (CDCl3, 500 MHz) δ 7.34 (t, J=7.5 Hz, 2H), 7.25 (t, J=7.5 Hz, 1H), 7.17 (d, J=7.5 Hz, 2H), 6.75 J=2.5 Hz, 1H), 6.68-6.40 (br, 2H), 4.27 (d, J=8.5 Hz, 1H), 3.94 (d, J=13.5 Hz, 1H), 3.81 (d, J=14.5 Hz, 1H), 3.77 (s, 3H), 3.27-3.16 (br, 1H), 3.06-3.01 (m, 1H), 2.55-2.45 (m, 2H), 2.32-2.24 (m, 1H), 2.13-2.04 (br, 1H), 1.11 (t, J=7.0 Hz, 3H); ESI MS m/z 282 [M+H]+.
Reaction SMILES: [NH3:1].[P:2]([Cl:7])([Cl:6])(Cl)(Cl)Cl>>[N:1]1[P:2]([Cl:7])([Cl:6])=[N:1][P:2]([Cl:7])([Cl:6])=[N:1][P:2]([Cl:7])([Cl:6])=[N:1][P:2]=1([Cl:7])[Cl:6]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: N
Product: ClP1(Cl)=NP(Cl)(Cl)=NP(Cl)(Cl)=NP(Cl)(Cl)=N1

Procedure:
A two-stage cascaded continuous reaction is effected as set forth in Example I, with the exception that NH3 feed is divided equally between the two reactors, instead of the total NH3 being fed to the first reactor. Into each reactor is metered a five to ten percent excess over the one-half molar equivalent of NH3, based on the moles of PCl5 introduced. A sample of product obtained under conditions as described in Example I, was collected and filtered. The filtrate was stripped of solvent in vacuo to obtain the product polymeric phosphonitrilic chloride, which contained 87.1% hexane soluble cyclic oligomers. The hexane insoluble linear fraction was a yellow oil. The cyclic portion was analyzed by gas chromatography and the distribution of cyclic portion was as follows: