Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:3]=1[CH:4]([OH:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:6]=1.[CH2:26]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH:37]=O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O)(=O)C.[BH4-].C([Na])#N>CO>[CH2:26]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH2:37][NH:1][C:2]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:3]=1[CH:4]([OH:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH:6]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2N)c1
Reactant: O=Cc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Agent: N#C[Na]
Agent: [BH4-]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2NCc2ccc(OCc3ccccc3)c(OCc3ccccc3)c2)c1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 75.5 %

Procedure:
In methanol (20 ml) were dissolved 2-amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (0.6 g) and 3,4-dibenzyloxybenzaldehyde (0.55 g). To the solution were added acetic acid (0.12 g) and cyano sodium borohydride (0.13 g). The mixture was stirred for 1.5 hour at 60° C. The reaction mixture was concentrated, to which were added water (50 ml) and ethyl acetate (80 ml), followed by extraction. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off to leave 2-(3,4-dibenzyloxybenzyl)amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (0.83 g) as colorless crystals, m.p.: 118-120° C.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]#[N:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:14]([O-:16])=[O:15])[CH:8]=2)[N:3]=1.[O:17]([C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>C(O)C>[N+:14]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[CH:2][C:11]([C:12]#[N:13])=[C:10]2[NH:28][C:27]1[CH:26]=[CH:25][C:24]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:30][CH:29]=1)([O-:16])=[O:15]
Reactant: Nc1ccc(Oc2ccccc2)cc1
Reactant: N#Cc1cc2cc([N+](=O)[O-])ccc2nc1Cl
Solvent: CCO
Solvent: O
Product: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Nc1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Yield: 103.9 %

Procedure:
A mixture of -chloro-6-nitroquinoline-3-carbonitrile (4.1 g, 17.6 mmol, 1.0 eq), 4-phenoxyaniline (2.6 g, 14.1 mmol, 0.8 eq) was dissolved in ethanol (40 mL). The reaction was heated to reflux for 2 hours, cooled to room temperature, poured into water (50 mL), and washed with ethyl acetate (50×2 mL). It was filtrated and dried in vacuum to give 6-nitro-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile (Compound 18) as a solid (5.6 g)
Reaction SMILES: [OH-].[Na+:2].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:33]=[CH:34][C:35]=1[O:36][CH2:37][C:38]1[N:39]=[C:40]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[O:41][C:42]=1[CH3:43])[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([O:22][CH:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24]([OH:26])=[O:25])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2>CC(O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:33]=[CH:34][C:35]=1[O:36][CH2:37][C:38]1[N:39]=[C:40]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[O:41][C:42]=1[CH3:43])[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([O:22][CH:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24]([O-:26])=[O:25])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2.[Na+:2]
Reactant: COc1cc(Cn2c3ccccc3c3c(OC(C(=O)O)c4ccccc4)cccc32)ccc1OCc1nc(-c2ccccc2)oc1C
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Product: COc1cc(Cn2c3ccccc3c3c(OC(C(=O)[O-])c4ccccc4)cccc32)ccc1OCc1nc(-c2ccccc2)oc1C

Procedure:
0.5 N sodium hydroxide solution (3.1 mL) was added to the solution of 980 mg of (+)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetic acid in 2-propanol (30 mL). 2-propanol was removed under reduced pressure, the residue was collected by filtration with a small amount of 2-propanol, and 850 mg of the subject compound was prepared as pale brown powder. Optical purity>99% ee (HPLC)
Reaction SMILES: [S:1]1[C:10]2[CH2:9][N:8]3[CH:11]=[CH:12][CH:13]=[C:7]3[CH2:6][NH:5][C:4]=2[CH:3]=[CH:2]1.C(N(CC)CC)C.[N+:21]([C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1)([O-:23])=[O:22]>C(Cl)Cl.C(OCC)(=O)C>[N+:21]([C:24]1[CH:25]=[CH:26][C:27]([C:28]([N:5]2[C:4]3[CH:3]=[CH:2][S:1][C:10]=3[CH2:9][N:8]3[CH:11]=[CH:12][CH:13]=[C:7]3[CH2:6]2)=[O:29])=[CH:31][CH:32]=1)([O-:23])=[O:22]
Reactant: c1cc2n(c1)Cc1sccc1NC2
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(c1ccc([N+](=O)[O-])cc1)N1Cc2cccn2Cc2sccc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3 mmol of 4,10-dihydro-5H-pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine in 10 ml of methylene chloride under argon is added 5 mmol of triethylamine followed by ice bath cooling. A solution of 3.3 mmol of 4-nitrobenzoyl chloride in 3 ml of methylene chloride is added dropwise. Following complete addition, the ice bath is removed and the reaction mixture stirred at room temperature for 2 hours. The volatiles are removed in vacuo to give a residue which is dissolved in ethyl acetate. The solution is washed with water, 2N citric acid, NaHCO3, and brine. The reaction mixture is dried with Na2SO4, filtered and evaporated in vacuo to give a solid which is purified by flash chromatography on silica gel to give desired product as a solid.
Reaction SMILES: Cl.[CH:2]([C@H:15]1[C@@H:20]([O:21][CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)[CH2:19][CH2:18][NH:17][CH2:16]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:37](O)(=[O:40])[CH2:38][CH3:39]>>[CH:2]([C@H:15]1[C@@H:20]([O:21][CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:24]=2)[CH2:19][CH2:18][N:17]([C:37](=[O:40])[CH2:38][CH3:39])[CH2:16]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CCC(=O)O
Reactant: FC(F)(F)c1cc(CO[C@H]2CCNC[C@H]2C(c2ccccc2)c2ccccc2)cc(C(F)(F)F)c1
Agent: Cl
Product: CCC(=O)N1CC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](C(c2ccccc2)c2ccccc2)C1

Procedure:
The compound (31.8 mg) obtained in Example 25 and propionic acid (9.0 μl) were reacted and treated in the same manner as in the method described in Example 33 to obtain the title compound.
Reaction SMILES: [CH2:1]([CH:9]1[C:17]([C:19]([F:22])([F:21])[F:20])(O)[C:16]2[C:11]3=[C:12]([O:23][CH2:24][CH2:25][N:10]13)[CH:13]=[CH:14][CH:15]=2)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.S(Cl)(Cl)=O>N1C=CC=CC=1>[CH2:1]([C:9]1[N:10]2[CH2:25][CH2:24][O:23][C:12]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]=1[C:19]([F:22])([F:20])[F:21])[C:11]2=3)[CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: OC1(C(F)(F)F)c2cccc3c2N(CCO3)C1CCc1ccccc1
Solvent: O=S(Cl)Cl
Solvent: c1ccncc1
Product: FC(F)(F)c1c(CCc2ccccc2)n2c3c(cccc13)OCC2
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of 5-phenethyl-6-(trifluoromethyl)-2,3,5,6-tetrahydro-[1,4]oxazino[2,3,4-hi]indol-6-ol (208 mg, 0.60 mmol) in pyridine (3 mL) was added thionyl chloride (142 mg, 1.2 mmol) at 0° C. After stirring for 2 h at 0° C., the resulting mixture was concentrated to yield 5-phenethyl-6-(trifluoromethyl)-2,3-dihydro-[1,4]oxazino[2,3,4-hi]indole.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[C:3]1[CH3:18].[CH2:19]([O:21][C:22](=[O:27])[C:23](Br)([CH3:25])[CH3:24])[CH3:20]>>[CH2:19]([O:21][C:22](=[O:27])[C:23]([CH3:25])([O:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:2]([CH3:1])[C:3]([CH3:18])=[C:4]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[CH3:24])[CH3:20]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: Cc1c(-c2ccccn2)c2cc(O)ccc2n1C
Product: CCOC(=O)C(C)(C)Oc1ccc2c(c1)c(-c1ccccn1)c(C)n2C

Procedure:
The above compound was prepared from 1,2-dimethyl-3-(2-pyridyl)-1H-indole-5-ol and 2-bromo-2-methyl-propanoic acid ethylester using a procedure analogous to that of Example 10.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4](O)=O.[NH:13]([C:15](=[S:17])[NH2:16])[NH2:14].O=P(Cl)(Cl)Cl>O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4]1[S:17][C:15]([NH2:16])=[N:13][N:14]=1
Reactant: NNC(N)=S
Reactant: COc1cccc(F)c1C(=O)O
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: COc1cccc(F)c1-c1nnc(N)s1
Temperature: 78 °C
Reaction time: 3 h
Yield: 93.6 %

Procedure:
A stirred mixture of 2-fluoro-6-methoxybenzoic acid (2 g, 11.7 6 mmol) and hydrazinecarbothioamide (1.607 g, 17.63 mmol) was cooled under nitrogen atmosphere in an ice bath and POCl3 (3.29 mL, 35.3 mmol) was added drop-wise. On completion of the addition, the reaction mixture was stirred at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath and quenched by addition of ice water (˜50 mL) to give a solid/gum-like mass. This solid was sonicated for 1.5 hours and the resulting suspension was diluted with a further 50 mL of water then slurried at room temperature for ˜16 hours. The solid was collected by vacuum filtration, rinsed with water, re-suspended in saturated NaHCO3(aq) (˜100 mL) and slurried for ˜30 minutes. The resulting solid was collected by vacuum filtration, then rinsed with water to afford the crude product as an off-white solid. The crude material was pre-absorbed onto silica gel and purified by flash chromatography using a 120 g silica cartridge with a 0-10% MeOH/DCM gradient as the eluent to afford the title compound as a pale yellow solid (1.265 g, 45% yield). LC-MS: Rt 0.77 min; MS m/z 226.1 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.48 (td, J=8.34, 6.57 Hz, 1H), 7.29 (s, 2H), 7.02 (d, J=8.08 Hz, 1H), 6.91-6.99 (m, 1H), 3.85 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[S:24][C:23]3[C:18](=[N:19][CH:20]=[CH:21][C:22]=3Cl)[CH:17]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1[NH:28][C:29]2[C:34]([CH:35]=1)=[CH:33][C:32]([NH2:36])=[CH:31][CH:30]=2>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[S:24][C:23]3[C:18](=[N:19][CH:20]=[CH:21][C:22]=3[NH:36][C:32]3[CH:33]=[C:34]4[C:29](=[CH:30][CH:31]=3)[NH:28][C:27]([CH3:26])=[CH:35]4)[CH:17]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2cc3nccc(Cl)c3s2)CC1
Reactant: Cc1cc2cc(N)ccc2[nH]1
Product: Cc1cc2cc(Nc3ccnc4cc(C(=O)N5CCN(C(=O)OC(C)(C)C)CC5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from 4-[7-chloro-thieno[3,2-b]pyridine-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester and 2-methyl-1H-indol-5-ylamine by a method analogous to Example 1C. MS: 492 (MH+); HPLC Rf: 5.42 min.; HPLC purity 95%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[N+:9]([O-])([OH:11])=[O:10].[OH-].[Na+]>S(=O)(=O)(O)O>[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: Cc1ccnc(N)c1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: Cc1cc(N)ncc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 15 h
Yield: 27 %

Procedure:
Concentrated sulfuric acid (120 mL) was cooled in an ice bath at 0° C. 2-Amino-4-methylpyridine (25.0 g, 230=mol) was added portionwise. A mixture of concentrated sulfuric acid (18 mL) and concentrated nitric acid (17.5 mL) was added with addition funnel over 1 h, maintaining the temperature at 0° C. The reaction mixture was then warmed to room temperature over 4 h. After 15 h, the reaction mixture was heated at 60° C. for 1 h, and then at 100° C. for 1 h. The reaction mixture was poured over ice and adjusted to pH 4-5 with 6 N aqueous sodium hydroxide. The 3-regioisomer was removed by steam distillation (9.11 g, 26%). The remaining residue was extracted with methylene chloride and dried over sodium sulfate, and the solvent was evaporated. The dark yellow solid was crystallized from acetonitrile and methanol to give 2-amino-4-methyl-5-nitropyridine (9.53 g, 27%) as a dark yellow solid: 1H NMR (300 MHz, CD3OD) δ2.53 (3H, s), 6.39 (1H, s), 8.76 (1H, s).
Reaction SMILES: [CH2:1]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH:24]([OH:31])[CH2:25]OS(C)(=O)=O)=[CH:19][CH:18]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:32])[CH2:4][CH3:5])[CH3:2].[NH3:33]>CO.CC(=O)OCC>[NH2:33][CH2:25][CH:24]([OH:31])[CH2:23][C:20]1[CH:21]=[CH:22][C:17]([C:14]2[N:13]=[C:12]([C:10]3[S:11][C:7]([CH2:6][N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[C:8]([CH3:32])[CH:9]=3)[O:16][N:15]=2)=[CH:18][CH:19]=1
Reactant: CCN(CC)Cc1sc(-c2nc(-c3ccc(CC(O)COS(C)(=O)=O)cc3)no2)cc1C
Reactant: N
Solvent: CO
Solvent: CCOC(C)=O
Product: CCN(CC)Cc1sc(-c2nc(-c3ccc(CC(O)CN)cc3)no2)cc1C

Procedure:
To a cooled (0° C.) solution of rac-3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-propane-1,2-diol (619 mg, 1.54 mmol) in THF (15 mL), DIPEA (399 mg, 3.08 mmol) followed by methansulfonyl chloride (247 mg, 2.16 mmol) is added. The mixture is stirred at 0° C. for 1 h, then at rt for 1 h. The mixture is diluted with DCM, washed with brine (3×50 mL), dried over MgSO4, filtered, concentrated and dried to give crude rac-methanesulfonic acid 3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-2-hydroxy-propyl ester (955 mg) as a light brown oil; LC-MS: tR=0.54 min; [M+1]+=480.10. b) A solution of the above rac-methanesulfonic acid 3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-2-hydroxy-propyl ester (600 mg, 1.33 mmol) in 7 M NH3 in methanol (10 mL) is stirred in a sealed vessel at 80° C. for 16 h. The mixture is diluted with EA and washed with water and brine. The organic extract is dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give the title compound (242 mg) as a pale yellow resin; LC-MS: tR=0.63 min; [M+1]+=400.93.
Reaction SMILES: [CH2:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].Cl.[NH2:15][C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27][C:28](=[O:41])[C@@H:29]([CH2:31][CH2:32][CH2:33][NH:34][C:35]([NH2:40])=[N:36][N+:37]([O-:39])=[O:38])[NH2:30])=[CH:22][CH:21]=1)=[O:17].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[NH2:15][C:16]([NH:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][NH:27][C:28](=[O:41])[C@@H:29]([CH2:31][CH2:32][CH2:33][NH:34][C:35]([NH2:40])=[N:36][N+:37]([O-:39])=[O:38])[NH:30][C:9](=[O:11])[C:8]2[CH:7]=[CH:6][C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[CH:13][CH:12]=2)=[CH:24][CH:25]=1)=[O:17]
Reactant: CCCCc1ccc(C(=O)O)cc1
Reactant: NC(=O)NCc1ccc(CNC(=O)[C@H](N)CCCNC(N)=N[N+](=O)[O-])cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Product: CCCCc1ccc(C(=O)N[C@H](CCCNC(N)=N[N+](=O)[O-])C(=O)NCc2ccc(CNC(N)=O)cc2)cc1
Yield: 33 %

Procedure:
Prepared analogously to Example 69a) from 4-butyl-benzoic acid, (R)-N-[[4-(aminocarbonylaminomethyl)phenyl]methyl]-N5 -[amino(nitroimino)methyl]-ornithinamide-hydrochloride and TBTU in a yield of 33% of theory.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([O:11][CH3:12])[C:4]=1[C:13]1[CH:18]=[C:17]([C:19](OCC)=[O:20])[N:16]=[C:15]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:14]=1.[BH4-].[Na+].Cl>C(O)C>[CH2:27]([O:26][C:24]([C:15]1[CH:14]=[C:13]([C:4]2[C:3]([O:2][CH3:1])=[CH:8][C:7]([O:9][CH3:10])=[CH:6][C:5]=2[O:11][CH3:12])[CH:18]=[C:17]([CH2:19][OH:20])[N:16]=1)=[O:25])[CH3:28]
Reactant: CCOC(=O)c1cc(-c2c(OC)cc(OC)cc2OC)cc(C(=O)OCC)n1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc(-c2c(OC)cc(OC)cc2OC)cc(CO)n1
Temperature: 45 °C
Reaction time: 1 h

Procedure:
Compound 12 (2.83 g, 7.27 mmol) was suspended in ethanol (140 mL), and the mixture was heated to 45° C. Sodium borohydride (0.29 g) was added, and the mixture was strirred for 1 h and allowed to cool to room temperature. pH of the solution was adjusted to 3 with 6 M HCl and concentrated. The residue was suspended in dichloromethane and washed with sat. NaHCO3. The organic layer was dried over Na2SO4 and purified on silica gel (eluent petroleum ether bp 40-60° C.:ethyl acetate:triethylamine, 2:5:1; v/v/v). ESI-MS: [M+H]+ 348.14 calc. for C18H22NO6+ 348.14.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:6]([O:8][CH3:9])=[O:7])#[N:2].C1C(=O)N([Br:21])C(=O)C1>C(Cl)(Cl)(Cl)Cl.[W]>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][Br:21])[C:6]([O:8][CH3:9])=[O:7])#[N:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1ccc(C)c(C#N)c1
Agent: [W]
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(CBr)c(C#N)c1
Reaction time: 2 h
Yield: 48.2 %

Procedure:
A mixture of methyl 3-cyano-4-methylbenzoate (1.78 g, 9.79 mmol) and NBS (1.92 g, 10.8 mmol) in CCl4 (150 mL) was irradiated with a 150W tungsten lamp at 50 C. for 2 h. The reaction was cooled, filtered, and concentrated. The residue was chromatographed (250 g silica, 10% EtOAc/hexanes to 15% EtOAc/hexanes) to give the title compound (1.20 g, 48%); IR(CHCl3: 1291, 1302, 1439, 1728 cm−1; NMR(300 MHz, CDCl3): 4.01 (s, 3H); 4.67 (s, 3H); 7.66 (d, 1H, J=8.1 Hz); 8.24 (d, 1H, J=8.7 Hz); 8.34 (s, 1H); MS(FD): 253.0.
Reaction SMILES: [NH2:1][C:2]1C=C(C(NCCCCCCCCCC)=O)C=C(C(NCCCCCCCCCC)=O)C=1.[CH2:34](C(Br)C([O-])=O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[I-].[Na+].[C:48](=[O:51])([O-])[O-:49].[K+].[K+]>CC(C)=O.CN(C=O)C>[C:35]1([CH2:34][O:49][C:48](=[O:51])[CH2:2][NH2:1])[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: O=C([O-])C(Br)Cc1ccccc1
Reactant: O=C([O-])[O-]
Reactant: CCCCCCCCCCNC(=O)c1cc(N)cc(C(=O)NCCCCCCCCCC)c1
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: NCC(=O)OCc1ccccc1

Procedure:
A mixture of 7.0 g (15.2 mmol) of 5-amino-N,N'-didecyl-1,3-benzenedicarboxamide, 9.7 ml of benzylbromoacetate, 4.6 (30.4 mmol) of sodium iodide and 4.2 g (30.4 mmol) of potassium carbonate in 150 ml of acetone and 50 ml of DMF was stirred at reflux for 26 hours. The reaction mixture was filtered and the solvents were removed from the filtrate at reduced pressure. The residue was purified by HPLC using 35% ethyl acetate-hexane. The pure fractions were combined and recrystallized from methylene chloride-ether to give 4.3 g (47% yield, mp 102°-104°) of N-[3,5-bis[decylamino)carbonyl]phenyl]glycine phenylmethyl ester. The nmr spectrum was consistent with the structure.
Reaction SMILES: [C:1]1(N)[NH:8][C:6](=[O:7])[NH:5][C:3](=[O:4])[N:2]=1.C1(N)NC(N)=NC(=[O:13])N=1>>[NH:8]1[C:1](=[O:13])[NH:2][C:3](=[O:4])[NH:5][C:6]1=[O:7]
Reactant: Nc1nc(=O)nc(N)[nH]1
Reactant: Nc1nc(=O)[nH]c(=O)[nH]1
Product: O=c1[nH]c(=O)[nH]c(=O)[nH]1
Yield: 6 %

Procedure:
The procedure of Example 10 was repeated with a 1-liter glass reactor and a nitrogen purge prior to the urea addition. After a two-hour stirring period, the crude cyanuric acid in the cooled slurry showed no sign of hydration at which time the slurry was vacuum filtered. The filter cake was then washed with water at which time the cyanuric acid hydrated. The hardened hydrated product was crushed and dried in an oven to produce a 93% yield of anhydrous cyanuric acid having an assay of 99+% purity and an ammelide content of 0.39% and an ammeline content of only 0.02%. Analysis of the filtrate showed an additional 6% yield of cyanuric acid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[N:28]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1)=[C:29]=[O:30]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:29](=[O:30])[NH:28][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1
Reactant: COc1ccc(N=C=O)cc1OC
Reactant: [O-][n+]1cc(Cl)c(C[C@H](O)c2ccc(OC(F)F)c(OCC3CC3)c2)c(Cl)c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: COc1ccc(NC(=O)O[C@@H](Cc2c(Cl)c[n+]([O-])cc2Cl)c2ccc(OC(F)F)c(OCC3CC3)c2)cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.2 %

Procedure:
To a stirred suspension of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (200 mg, 0.476 mmol) in anhydrous DCM (10 ml), a solution of DMAP (87 mg, 0.714 mmol) and 4-isocyanato-1,2-dimethoxybenzene (171 mg, 0.952 mmol) in anhydrous DCM (5 ml) was added dropwise within 10 minutes. The reaction mixture was stirred at RT overnight. After 18 hours, the reaction mixture was diluted with DCM (10 ml) and washed with HCl 0.5M. The organic layer was dried over Na2SO4 and evaporated. The crude material was purified by flash chromatography on silica gel (EtOAc 100%) affording the desired product as a white solid (200 mg, 0.334 mmol, 70.1% yield, [α]D=−27.6, c=0.45, DCM).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[C:13]([C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:24]=1)[CH2:20][Zn+])([CH3:16])([CH3:15])[CH3:14].Cl>O1CCCC1.CC(OC)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:13]([C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:24]=1)[CH2:20][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6])([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)c1cc(C[Zn+])cc(C(C)(C)C)c1
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [Br-]
Solvent: C1CCOC1
Solvent: COC(C)(C)C
Product: COC(=O)c1ccnc(Cc2cc(C(C)(C)C)cc(C(C)(C)C)c2)c1
Temperature: 60 °C
Reaction time: 1 h
Yield: 90.1 %

Procedure:
To a solution of methyl 2-chloroisonicotinate (4 g, 23.31 mmol) and Pd(PPh3)4 (0.539 g, 0.47 mmol) in tetrahydrofuran (120 mL) under nitrogen in a dried flask was added a freshly prepared solution of (3,5-di-tert-butylbenzyl)zinc(II) bromide (11.08 g, 31.78 mmol) in tetrahydrofuran (46 mL). The resulting bright yellow solution was heated to 60° C. for 35 min, then stirred at room temperature for 1 h. The reaction was quenched by addition of methanol (50 mL). The solution was diluted with EtOAc and washed with NH4Cl. The organic layer was dried over MgSO4, filtered and evaporated to yield a brown oil. The crude was redissolved in MTBE (180 mL) and solids were filtered off. Hydrogen chloride (4 M in dioxane, 6.42 mL, 25.66 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 10 min. The solid was collected by filtration and washed with MTBE. Redissolved in MTBE/satd NaHCO3. The phases were separated, the organic phase dried over Na2SO4, filtered and evaporated to yield methyl 2-(3,5-di-tert-butylbenzyl)isonicotinate (7.132 g, 90%) as a brown oil. 1H NMR (600 MHz, cdcl3) δ 1.28 (s, 18H), 3.89 (s, 3H), 4.19 (s, 2H), 7.11 (d, 2H), 7.27 (t, 1H), 7.64 (dd, 1H), 7.71 (s, 1H), 8.68 (d, 1H). MS m/z 340 (M+H)+