Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[H-].[Na+].Cl[CH2:13][CH2:14][O:15][CH3:16]>CN(C=O)C>[CH3:16][O:15][CH2:14][CH2:13][O:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: COCCCl
Reactant: O=Cc1ccccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCOc1ccccc1C=O
Temperature: 70 °C
Reaction time: 48 h
Yield: 16.6 %

Procedure:
To a solution of 2-hydroxybenzaldehyde (6.11 g, 0.05 mol) in DMF (50 ml) under argon in an ice bath was added NaH (2.0 g, 0.05 mol, 60% dispersion in mineral oil), followed 1 hour later by 2-chloroethylmethyl ether (4.73 g, 0.05 mol). The reaction mixture was allowed to stand for about 2 days, then was heated at 70° C. for 7 hours. The reaction mixture was stripped to dryness, the residue was partitioned between water and CHCl3, the layers were separated and the aqueous layer was extracted with CHCl3 (2×75 ml). The product appeared to be in both layers, thus they were concentrated in vacuo and the residue was purified by column chromatography on silica gel eluting with ether to afford 1.5 g of 2-[2-(methoxy)ethoxy]benzaldehyde.
Reaction SMILES: [CH2:1]([N:8]([CH3:25])[C:9]([CH2:11][CH2:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20](=[O:24])[C:21]([OH:23])=O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([N:28](CC)CC)[CH3:27].ClC(OCC(C)C)=O.C(N)C>C1COCC1.O>[CH2:1]([N:8]([CH3:25])[C:9]([CH2:11][CH2:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20](=[O:24])[C:21]([NH:28][CH2:26][CH3:27])=[O:23])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCN(CC)CC
Reactant: CN(Cc1ccccc1)C(=O)CCC(=O)N1CCC[C@H]1C(=O)C(=O)O
Agent: CC(C)COC(=O)Cl
Agent: CCN
Solvent: O
Solvent: C1CCOC1
Product: CCNC(=O)C(=O)[C@@H]1CCCN1C(=O)CCC(=O)N(C)Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of 2 [(2S)-1-[3-(N-benzyl-N-methylcarbamoyl)propanoyl]pyrrolidin-2-yl]-2-oxoacetic acid (98 mg) in THF (3 ml) was cooled to -20° C. Triethylamine (188 μl) and isobutyl chloroformate (77 μl) were added dropwise to the solution. The mixture was stirred for 20 mins at the same temperature. An aq. solution of ethylamine (70%; 200 μl) was added dropwise to the solution at the same temperature. The solution was stirred for 1 hr, while the temperature of the solution was raised to room temperature gradually. Water was added to the reaction solution. The mixture was extracted with EtOAc. The extract was washed, dried and evaporated. The residue was purified by column chromatography on silica gel (CH2Cl2 --CH3OH) to give the title compound (62 mg) having the following physical data:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=1[O:5][CH2:6][CH:7]1[NH:11][CH2:10][CH2:9][S:8]1.[CH3:16][S:17](Cl)(=[O:19])=[O:18]>N1C=CC=CC=1.OS(O)(=O)=O>[CH3:16][S:17]([N:11]1[CH2:10][CH2:9][S:8][CH:7]1[CH2:6][O:5][C:4]1[CH:12]=[CH:13][CH:14]=[CH:15][C:3]=1[O:2][CH3:1])(=[O:19])=[O:18]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccccc1OCC1NCCS1
Agent: O=S(=O)(O)O
Solvent: c1ccncc1
Product: COc1ccccc1OCC1SCCN1S(C)(=O)=O
Yield: 89.3 %

Procedure:
A solution of 2-(o-methoxyphenoxy)methyl-thiazolidine (1.83 g) in pyridine (6 ml) is treated with methane sulphonyl chloride (1.2 g) at room temperature. After 4 hours the mixture is diluted with 2N H2SO4, extracted with Et2O, to afford after the usual work-up 2.2 g of 3-methanesulphonyl-2-(o-methoxyphenoxy)methyl-thiazolidine m.p. 118°-120° C.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Cl:6][C:7]([Cl:11])([Cl:10])[CH:8]=[O:9]>CCCCCCC>[Cl:6][C:7]([Cl:11])([Cl:10])[CH:8]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[OH:9]
Reactant: c1ccsc1
Reactant: O=CC(Cl)(Cl)Cl
Solvent: CCCCCCC
Product: OC(c1cccs1)C(Cl)(Cl)Cl
Yield: 20 %

Procedure:
Thiophene (4.2 g, 50 mmol) and trichloroacetaldehyde (7.35 g, 50 mmol) were dissolved in n-heptane (25 ml). The solution was heated under reflux for 3.5 hr. under a Soxleht apparatus in which Amberlyst 15 (4.2 g) had been placed. After cooling, the n-heptane solution was concentrated, and the residue was purified by distillation to give 2.32 g of α-trichloromethyl-2-thiophenemethanol boiling at 98°-100° C./1.0 mmHg.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:30][C@H:31]2[CH2:35][C:34]([F:37])([F:36])[CH2:33][C@@H:32]2[C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)=[CH:4][C:5]([F:29])=[C:6]([S:8]([N:11](CC2C=CC(OC)=CC=2OC)[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:3]([O:30][C@H:31]2[CH2:35][C:34]([F:37])([F:36])[CH2:33][C@@H:32]2[C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)=[CH:4][C:5]([F:29])=[C:6]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:9])=[O:10])[CH:7]=1
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2cc(Cl)c(O[C@H]3CC(F)(F)C[C@@H]3c3ccnn3C)cc2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cn1nccc1[C@H]1CC(F)(F)C[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)cc1Cl
Yield: 98.1 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 5-chloro-4-{[(1S*,2R*)-4,4-difluoro-2-(1-methyl-1H-pyrazol-5-yl)cyclopentyl]oxy}-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide (316 mg, 0.495 mmol) prepared in Example 146a, triethylsilane (0.30 mL), trifluoroacetic acid (2.0 mL) and dichloromethane (3.0 mL), to yield the title compound (237 mg, 98%) as a colorless solid.
Reaction SMILES: [N:1]1[CH2:2][CH2:3][CH2:4][N:5]2[C:9]3[CH:10]=[C:11]([NH2:14])[CH:12]=[CH:13][C:8]=3[S:7][C:6]=12.C(O)(=O)C.[O-:19][C:20]#[N:21].[K+].[OH-].[NH4+]>O>[N:1]1[CH2:2][CH2:3][CH2:4][N:5]2[C:9]3[CH:10]=[C:11]([NH:14][C:20]([NH2:21])=[O:19])[CH:12]=[CH:13][C:8]=3[S:7][C:6]=12
Reactant: Nc1ccc2c(c1)N1CCCN=C1S2
Reactant: N#C[O-]
Agent: [K+]
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: NC(=O)Nc1ccc2c(c1)N1CCCN=C1S2
Temperature: 10 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 3 parts of 3,4-dihydro-2-H-pyrimido[2,1-b]benzothiazol-7-amine in 16 parts of acetic acid are added 32 parts of water. Then there is added dropwise a solution of 1.46 parts of potassium cyanate in 32 parts of water (slightly exothermic reaction). Upon completion, stirring is continued overnight at room temperature. The reaction mixture is alkalized with ammonium hydroxide and the whole is stirred while cooling at 10° C. The precipitated product is filtered off and crystallized twice: first from 2-methoxyethanol and then from 1-butanol, yielding 0.6 parts of N-(3,4-dihydro-2H-pyrimido[2,1-b]benzothiazol-7-yl)urea; mp. 245.9° C.
Reaction SMILES: O=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:13][C:14]([OH:16])=O.O.[NH2:18][NH2:19]>C(O)C>[N:18]1[NH:19][C:14](=[O:16])[CH2:13][CH:3]2[CH2:4][CH2:5][CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:2]=12
Reactant: O=C(O)CC1CCCc2ccccc2C1=O
Reactant: NN
Solvent: CCO
Solvent: O
Product: O=C1CC2CCCc3ccccc3C2=NN1

Procedure:
A mixture of the compound of formula (Dc), 2-(5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-yl)acetic acid, (5.7 g, 26.1 mmol) and hydrazine hydrate (1.6 mL, 32.7 mmol) in 20 mL of ethanol was refluxed for 2 h, cooled and filtered (washed with small amount of EtOH) to give the compound of formula (Dd), 4a,5,6,7-tetrahydro-2H-benzo[6,7]cyclohepta[c]pyridazin-3(4H)-one, as a white solid (4.7 g, 84%); 1H NMR (300 MHz, CDCl3) δ: 8.61 (bs, 1H), 7.53-7.14 (m, 4H), 2.98-2.75 (m, 3H), 2.58 (dd, J=15.3, 16.8 Hz, 1H), 2.31 (dd, J=12.0, 16.8 Hz, 1H), 1.96-1.59 (m, 4H); LC-MS: purity: 100%; MS (m/e): 215 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[CH3:9][C:10]([CH3:14])(O)[C:11]#[N:12]>>[CH3:9][C:10]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1)([CH3:14])[C:11]#[N:12]
Reactant: CC(C)(O)C#N
Reactant: Cc1ccc(N)cc1
Product: Cc1ccc(NC(C)(C)C#N)cc1
Temperature: 80 °C
Reaction time: 4 h
Yield: 99 %

Procedure:
A mixture of p-toluidine (1.07 g, 10 mmol) and acetone cyanohydrin (10 ml) was heated to 80° C. and stirred for 4 h. The medium was concentrated and dried under vacuum to yield 2-methyl-2-(4-methylphenyl)aminopropanenitrile, 5a (1.72g, 9.9 mmol, 99%) as brown solid.
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].[O:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[CH2:11][OH:12]>N1C=CC=CC=1>[O:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[CH2:11][O:12][S:1]([CH3:4])(=[O:3])=[O:2]
Reactant: OC[C@@H]1CCCO1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)OC[C@@H]1CCCO1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Mesylchloride (12.1 g) was added to a mixture of (S)-1-(Tetrahydro-furan-2-yl)-methanol (10.0 g) and pyridine (55 mL) at −15° C. and stirred for 1.5 hours at room temperature. The mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with a solution of potassium hydrogensulfate (20%) and with a solution of saturated sodium hydrogencarbonate, dried over magnesium sulfate and concentrated.
Reaction SMILES: [CH:1]([C:3]1[CH:16]=[CH:15][C:6]([O:7][CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[C:5]([O:17][CH3:18])[CH:4]=1)=[O:2].[N+:19]([O-])([OH:21])=[O:20].O.[K+].[Br-]>C(Cl)Cl>[CH:1]([C:3]1[C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:6]([O:7][CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[C:5]([O:17][CH3:18])[CH:4]=1)=[O:2]
Reactant: O=[N+]([O-])O
Reactant: COC(=O)CCCOc1ccc(C=O)cc1OC
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: COC(=O)CCCOc1cc([N+](=O)[O-])c(C=O)cc1OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a pale pink solution of methyl 4-(4′-formyl-2′-methoxyphenoxy)butanoate (4) (3 g, 12.3 mmol) in DCM (20 cm3) was added dropwise, at 0° C. fuming nitric acid (1.5 cm3, 37.0 mmol). The resulting green solution was stirred at 00° C. for a further 30 mins before being allowed to spontaneously warm to r.t., where it remained for 3 hours. The subsequent bright yellow suspension was poured onto iced water (50 cm3) and extracted with DCM (3×30 cm3). The combined organic phase was washed with sat. NaHCO3 solution (2×50 cm3), followed by water (2×50 cm3) before being dried and concentrated in vacuo providing a bright yellow solid. The desired compound 5 was used without further purification (2.48 g, 68%). A small amount of material (250 mg, 0.84 mmol) was purified via column chromatography (SiO2, CH2Cl2) so that complete characterisation data could be obtained, m.p. 75° C. [lit. (D. L. McMinn and M. M. Greenberg, Tetrahedron, 1996, 52, 3827.) m.p. 76-78° C.]. Found C, 52.7; H, 5.2; N, 4.8; C13H15NO7 requires C, 52.5; H, 5.1; N, 4.7%; Rf 0.44 (SiO2, CH2Cl2); νmax (KBr disc)/cm−1 3100-2700 (m), 1735 (s), 1690 (s), 1290, 1220; 6, (200 MHz, CDCl3) 2.23 (2H, q, J=7.1 Hz, CH2), 2.57 (2H, t, J=7.1 Hz, CH2), 3.71 (3H, s, OCH3), 3.99 (3H, s, OCH3), 4.21 (2H, t, J=7.1 Hz, CH2), 7.40 (1H, s, H-3′), 7.61 (1H, s, H-6′), 10.44 (1H, s, CHO) ppm; δC (100 MHz, CDCl3) 24.1 (CH2), 30.2 (CH2), 51.8 (OCH3), 56.6 (OCH3), 59.6 (CH2), 108.1 (CH), 109.9 (CH), 125.5, 143.8, 151.7, 153.4, 173.2 (COOCH3), 187.8 (CHO) ppm; m/z (FAB) 298 [(MH+), 40%].
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[S:25][CH:26]=[CH:27][N:28]=3)=[CH:20][CH:19]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:29])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([S:38]([CH3:37])(=[O:40])=[O:39])[CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[S:25][CH:26]=[CH:27][N:28]=3)=[CH:22][CH:23]=2)[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)COc1cccc(CNCc2ccc(-c3nccs3)cc2)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)COc1cccc(CN(Cc2ccc(-c3nccs3)cc2)S(C)(=O)=O)c1

Procedure:
A solution of ({3-[(4-thiazol-2-yl-benzylamino)-methyl]-phenoxy}-acetic Acid tert-butyl ester (0.045 g, 0.109 mmol), triethylamine (16.8 mL, 0.120 mmol) and methanesulfonyl chloride (8.6 ml, 0.11 mmol) in 2 mL CH2Cl2 was stirred at room temperature for 2 hours. The reaction was quenched with water. The aqueous solution was washed with CH2Cl2 and the organic solution was dried over Na2SO4, filtered, and concentrated. The product was purified via flash chromatography on silica gel (1/1 EtOAc/Hexanes) to afford the title compound of Step B as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, 2H), 7.85 (s, 1H), 7.35 (m, 3H), 7.32 (m, 1H), 6.80-6.90 (m, 3H), 4.48 (s, 2H), 4.36 (s, 2H), 4.29 (s, 2H), 2.79 (s, 3H), 1.47 (s, 9H); MS 489 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:18])[C:5]([NH2:17])=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=1[Cl:16].[F:19][C:20]([F:31])([F:30])[C:21]([F:29])([F:28])[C:22]([F:27])([F:26])[C:23](O)=O.Cl>>[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=2[Cl:16])=[CH:6][C:5]2[NH:17][C:23]([C:22]([F:26])([F:27])[C:21]([F:28])([F:29])[C:20]([F:31])([F:30])[F:19])=[N:18][C:4]=2[CH:3]=1
Reactant: O=C(O)C(F)(F)C(F)(F)C(F)(F)F
Reactant: Nc1cc(Cl)c(Oc2cccc(Cl)c2Cl)cc1N
Agent: Cl
Product: FC(F)(F)C(F)(F)C(F)(F)c1nc2cc(Cl)c(Oc3cccc(Cl)c3Cl)cc2[nH]1
Temperature: 110 °C
Reaction time: 8 h

Procedure:
Compound number 140 (i.e., 6-chloro-5-(2,3-dichlorophenoxy)-2-heptafluoropropylbenzimidazole) was prepared as follows. 4-chloro-5-(2,3-dichlorophenoxy)benzene-1,2-diamine (150 mg, 0.49 mmol, 1.00 equiv), heptafluorobutanoic acid (15 mL) and hydrogen chloride (3 mL) was placed into a 100-mL round-bottom flask. The resulting solution was stirred overnight at 110° C. in an oil bath. The reaction mixture was cooled to room temperature. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×100 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). The crude product was re-crystallized from EA/hexane in the ratio of 1/1. This resulted in 63.4 mg (27%) of 6-chloro-5-(2,3-dichlorophenoxy)-2-heptafluoropropylbenzimidazole as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:25]#[N:26])=[C:4]([CH:22]=[CH:23][CH:24]=1)[O:5][CH2:6][C:7]([CH3:21])([CH3:20])[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)=[O:9].O=[C:28]([CH3:35])[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>>[NH2:26][C:25]1[C:3]2[C:2](=[CH:24][CH:23]=[CH:22][C:4]=2[O:5][CH2:6][C:7]([CH3:21])([CH3:20])[C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[O:9])[N:1]=[C:28]([CH3:35])[C:29]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31]
Reactant: CCOC(=O)CC(C)=O
Reactant: COc1cccc(CNC(=O)C(C)(C)COc2cccc(N)c2C#N)c1
Product: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)C(=O)NCc3cccc(OC)c3)c2c1N

Procedure:
Prepared as in Example 2a from 3-(3-amino-2-cyanophenoxy)-N-(3-methoxybenzyl)-2,2-dimethylpropanamide (Example 46b) and ethyl 3-oxobutanoate as a yellow solid (42%). MS 466 (MH+).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:29]=[CH:30][C:31]([C:34]#[N:35])=[N:32][CH:33]=4)=[C:14]([CH2:16][O:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.[N-:36]=[N+:37]=[N-:38].[Na+].Cl.C(N(CC)CC)C>CN(C)C=O>[NH:36]1[C:34]([C:31]2[N:32]=[CH:33][C:28]([C:13]3[N:9]4[N:10]=[CH:11][CH:12]=[C:7]([N:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)[C:8]4=[N:15][C:14]=3[CH2:16][O:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)=[CH:29][CH:30]=2)=[N:35][N:38]=[N:37]1
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccc(-c2c(COc3ccc4ccccc4n3)nc3c(N4CCOCC4)ccnn23)cn1
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: c1ccc2nc(OCc3nc4c(N5CCOCC5)ccnn4c3-c3ccc(-c4nnn[nH]4)nc3)ccc2c1

Procedure:
A solution of compound 83c (200 mg, 0.430 mmol), sodium azide (85 mg, 1.31 mmol) and triethylamine hydrochloride (300 mg, 2.17 mmol) in N,N-dimethylformamide (3 mL) was stirred for 2 h at 110° C. The reaction was quenched by the addition of 10 mL of water. The solids were collected by filtration. The crude product was purified by flash column chromatography on silica gel (methanol/DCM, 1:200-1:10) to afford title compound 33 as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 9.13 (s, 1H), 8.52-8.50 (m, 1H), 8.38-8.36 (m, 1H), 8.26-8.22 (m, 2H), 7.88 (d, J=7.6 Hz, 1H), 7.64-7.59 (m, 2H), 7.43-7.39 (m, 1H), 7.04 (d, J=8.8 Hz, 1H), 6.49-6.48 (m, 1H), 5.68 (s, 2H), 4.05-3.98 (m, 4H), 3.85-3.75 (m, 4H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C26H22N10O2: 507.2 (M+H). Found: 507.1.
Reaction SMILES: C([O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9](=[O:21])[N:10]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:11]2)=[CH:7][C:6]=1[O:22][C:23](=[O:25])[CH3:24])(=O)C.N1CCOCC1>CN(C)C=O>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([N:10]2[C:9](=[O:21])[C:8]3[C:12](=[CH:13][C:5]([OH:4])=[C:6]([O:22][C:23](=[O:25])[CH3:24])[CH:7]=3)[CH2:11]2)=[CH:19][CH:18]=1
Reactant: CC(=O)Oc1cc2c(cc1OC(C)=O)C(=O)N(c1ccc(Cl)cc1)C2
Solvent: CN(C)C=O
Solvent: C1COCCN1
Product: CC(=O)Oc1cc2c(cc1O)CN(c1ccc(Cl)cc1)C2=O
Temperature: 0 °C

Procedure:
A solution of acetic acid 6-acetoxy-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-1H-isoindol-5-yl ester (0.5 g) in dry N,N-dimethylformamide (15 ml) was treated with morpholine (0.13 ml) at 0-5° C. and stirred then for an hour at room temperature. The reaction was poured into ice water and filtered.