Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(O[CH2:6][CH2:7]/[CH:8]=[CH:9]/[CH2:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:12])(=O)=O.[NH3:28].O.O>CN(C=O)C>[NH2:28][CH2:6][CH2:7]/[CH:8]=[CH:9]/[CH2:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21](=[O:22])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:12]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1NC(=O)C/C=C/CCOS(C)(=O)=O
Reactant: N
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)Nc1ccccc1NC(=O)C/C=C/CCN
Reaction time: 0.5 h
Yield: 88 %

Procedure:
To a solution of (E)-6-(2-(tert-butoxycarbonylamino)phenylamino)-6-oxohex-3-enyl methanesulfonate (358 mg, 0.9 mmol) in DMF (5 mL) was added NH3.H2O (20 mL) at 0° C. and stirred at the same temperature for 0.5 hour, then the reaction mixture was stirred at room temperature for 12 hr, then water (100 mL) was added, the mixture was extracted with DCM (3×50 mL), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give the desired compound of (E)-tert-butyl 2-(6-aminohex-3-enamido)phenylcarbamate (100 mg, 88%) as a white solid after purification by column chromatography (eluent: DCM:MeOH=50:1).
Reaction SMILES: [C:1]1([CH3:8])[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16](O)([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:12][CH:11]=1>FC(F)(F)C(O)=O>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([C:3]2[CH:4]=[CH:5][C:6]([OH:7])=[C:1]([CH3:8])[CH:2]=2)([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:12][CH:11]=1
Reactant: CCC(O)(CC)c1ccc(Br)cc1
Reactant: Cc1ccccc1O
Solvent: O=C(O)C(F)(F)F
Product: CCC(CC)(c1ccc(Br)cc1)c1ccc(O)c(C)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 94.4 %

Procedure:
o-Cresol (890 mg, 8.23 mmol) was added to a solution of 3-(4-bromo-phenyl)-pentan-3-ol (Example 143-(1); 2.0 g, 8.23 mmol) in trifluoroacetic acid (20 mL), and the mixture was stirred at room temperature for five hours. Then, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 30:70) to give the target compound as a colorless oil (2.59 g, 94%).
Reaction SMILES: [CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]#[CH:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:15]1[O:17][CH2:16]1.S(=O)(=O)(O)O>C1COCC1>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]([C:13]#[C:14][CH2:15][CH2:16][OH:17])=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: C#Cc1ccc(C2CCCCC2)cc1
Reactant: C1CO1
Agent: O=S(=O)(O)O
Solvent: C1CCOC1
Product: OCCC#Cc1ccc(C2CCCCC2)cc1
Reaction time: 1 h

Procedure:
To a solution of 153 g of ethylbromide in 160 ml of abs. THF, is added a suspension of 36 g of magnesium turning in 330 ml of THF, (to obtain a solution of ethyl magnesium bromide) and the reaction mixture cooled to 0° to 5°. To the reaction mixture is then added, dropwise, a solution of 214 g of p-cyclohexylphenylacetylene in 420 ml of abs. THF, over a period of one hour. The resulting thick suspension is diluted with 200 of abs. THF and then refluxed for 1.5 hours. The reaction mixture is then cooled to 0°, and a solution of 62 g ethylene oxide in 420 ml of abs. THF added thereto, dropwise, over a period of one hour. After addition is completed, the reaction mixture is refluxed for 2.5 hours, then decomposed by adding dilute sulfuric acid (5%), and extracted with ether. The combined ether extracts are washed with water, then brine, and evaporated i.v. to dryness to obtain a residue from which is crystallized 4-(p-cyclohexylphenyl)-3-butyn-1 -ol, m.p. 56° - 59° from pentane.
Reaction SMILES: [NH2:1][C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C1C=C(O[C:19](OC2N=CC=CC=2)=[S:20])N=CC=1>C(Cl)Cl>[N:1]([C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1)=[C:19]=[S:20]
Reactant: S=C(Oc1ccccn1)Oc1ccccn1
Reactant: Cc1c(N)ccc2cc[nH]c12
Solvent: ClCCl
Product: Cc1c(N=C=S)ccc2cc[nH]c12
Temperature: 25 °C
Reaction time: 2 h
Yield: 69.9 %

Procedure:
To a solution of 6-amino-7-methylindole (1.0 g, 6.84 mmol) in methylene chloride (50 mL) is added di-2-pyridyl thionocarbonate (1.59 g, 6.84 mmol). The resulting solution is stirred at room temperature for two hours followed by removal of the methylene chloride by rotary evaporation. The crude material is purified via silica gel column chromatography using 10% ethyl acetate/hexane as the eluting solvent. The product containing fractions are combined and the solvents removed by rotary evaporation to yield 0.90 g of 6-isothiocyanato-7-methylindole as a white solid (70% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:27][CH2:28][C:29]([OH:31])=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:32].C[N:34]1CCO[CH2:36][CH2:35]1.CN1CCCC1=O.Cl.CN(C)CCCN=C=NCC.C(N)C>CCOC(C)=O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:27][CH2:28][C:29]([NH:34][CH2:35][CH3:36])=[O:31])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:32]
Reactant: CN1CCOCC1
Reactant: Cc1cc(F)ccc1-c1nc(NCC(=O)O)nc2c1ccc(=O)n2-c1c(F)cccc1F
Agent: CCN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CCNC(=O)CNc1nc(-c2ccc(F)cc2C)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Reaction time: 1 h
Yield: 68.1 %

Procedure:
The product of Example 191 (50 mg, 0.11 mmol), n-hydroxybenzotriazole (21 mg, 0.34 mmol), 1-methylmorpholine (19 uL, 0.172 mmol), N-methylpyrrolidinone (2.5 mmol) were dissolved together, then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (66 mg, 0.34 mmol) was added, stirred 1 h, and then ethylamine (2 M in THF) (1.0 mL, 2.0 mmol) was added and the reaction was stirred at 23° for 16 h, diluted with EtOAc (50 mL), and washed with 10% aq citric acid (2×20 mL), H2O (20 mL), and satd aq NaCl (20 mL), dried (MgSO4) concentrated and purified by chromatotron chromatography (CH2Cl2/CH3OH) to afford 35 mg of the title compound 2-[[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7,8-dihydro-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-ethylacetamide as a white powder. mp=250-253 (dec). LC MS (m/e)=468.2 (MH+). Rt=1.87 min.
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([OH:9])[N:3]=1.CC#N.[C:13](=[S:22])(Cl)[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl>[NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]([C:13](=[S:22])[O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:4](=[O:9])[N:3]=1
Reactant: S=C(Cl)Oc1ccccc1
Reactant: Nc1nc(O)ncc1F
Solvent: ClCCl
Solvent: CC#N
Product: Nc1nc(=O)n(C(=S)Oc2ccccc2)cc1F
Temperature: 65 °C
Reaction time: 1.33 h
Yield: 29.6 %

Procedure:
A 25 mL screw-top vial was charged with 4-amino-5-fluoropyrimidin-2-ol (99.7 mg, 0.772 mmol) and CH3CN (3 mL). BSA (0.284 mL, 1.16 mmol) was added, the vial was capped and the resulting heterogenous mixture was agitated on a rotary shaker at 65° C. for 80 min. The resulting clear and colorless solution was cooled to room temperature. O-Phenyl carbonochloridothioate (0.118 mL, 0.853 mmol) was added, and the reaction was agitated on a rotary shaker at 65° C. for 15 h. After cooling to room temperature, the crude material was diluted with CH2Cl2 (100 mL) and washed with saturated aqueous sodium chloride (satd aq NaCl) solution (50 mL×2). The organic solution was then dried over Na2SO4, filtered, and concentrated in vacuo. The green/brown residue was then purified by normal phase chromatography (gradient, 0 to 35% methyl alcohol (MeOH)/CH2Cl2) to afford O-phenyl 4-amino-5-fluoro-2-oxopyrimidine-1(2H)-carbothioate (60.7 mg, 30%) as an 85% pure brown solid: mp 113-116° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.44 (d, J=7.2 Hz, 1H), 8.28 (s, 1H), 7.56-7.48 (m, 2H), 7.40-7.33 (m, 1H), 7.27-7.21 (m, 2H); ESIMS m/z 266 ([M+H]+).
Reaction SMILES: Cl.[NH2:2][OH:3].[C:4]([C:6]([NH:9][C:10]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[O:22][CH2:23][C:24]1[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=1)=[O:11])([CH3:8])[CH3:7])#[N:5].C(=O)([O-])[O-].[K+].[K+]>C(O)C.C(OCC)(=O)C>[OH:3][NH:2][C:4]([C:6]([NH:9][C:10]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[O:22][CH2:23][C:24]1[CH:25]=[N:26][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:28][CH:29]=1)=[O:11])([CH3:8])[CH3:7])=[NH:5]
Reactant: NO
Reactant: CC(C)(C#N)NC(=O)c1ccc2ccccc2c1OCc1ccc(C(F)(F)F)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CC(C)(NC(=O)c1ccc2ccccc2c1OCc1ccc(C(F)(F)F)nc1)C(=N)NO
Temperature: 25 °C
Yield: 10.3 %

Procedure:
0.16 g hydroxylamine hydrochloride was added to a room temperature solution of 0.28 g 1-(6-trifluoromethyl-pyridin-3-yl-methoxy)-naphthalene-2-carboxylic acid (cyano-dimethyl-methyl)-amide and 0.50 g potassium carbonate in 5 ml 95% ethanol, and the resulting mixture was heated at reflux for 24 h. The reaction mixture was cooled to room temperature, diluted with 100 ml ethyl acetate, and was washed twice with 100 ml sat. sodium hydrogen carbonate solution and 100 ml brine. The combined organic layers were dried over sodium sulphate, and concentrated in vacuo to give an orange oil. Purification of the residue by RP-HPLC afforded 0.031 g of 1-(6-trifluoromethyl-pyridin-3-yl-methoxy)-naphthalene-2-carboxylic acid [1-(N-hydroxycarbamimidoyl)-1-methyl-ethyl]-amide as a colorless foam.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[N:6]=[CH:7][CH:8]=[N:9]2)([O-])=O.O>CC(O)=O.[Fe]>[NH2:1][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[N:6]=[CH:7][CH:8]=[N:9]2
Reactant: O=[N+]([O-])c1cccc2nccnc12
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: Nc1cccc2nccnc12
Yield: 61.3 %

Procedure:
To a three neck 250 mL round bottom flask equipped with a reflux condenser and nitrogen inlet was added 5-nitro-quinoxaline (4 g, 22.8 mmol) dissolved in HOAc (60 mL). The mixture was heated to boiling, removed from heat, and solid Fe powder (3.83 g, 68.6 mmol) was added. Vigorous boiling was observed. The reaction mixture was heated at reflux 10 minutes and then poured into H2O (100 mL) and ice. The aqueous solution was filtered and basified to pH>10 with 1 M NaOH, and extracted in EtOAc (3×200 mL). The organic layers were combined, dried over Na2SO4, and concentrated. The resulting oil was purified by column chromatography (40% EtOAc/Hexanes) yielding 2.03 g (61%) of an orange solid: mp 87-90° C.
Reaction SMILES: S(Cl)(Cl)=O.[N+:5]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][C:16]=1[CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[C:11]([OH:13])=O)([O-:7])=[O:6].[CH2:23]([O:30][C:31]1[CH:32]=[CH:33][C:34]2[CH:38]=[C:37]([N:39]([CH3:41])[CH3:40])[S:36][C:35]=2[CH:42]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[N+:5]([C:8]1[CH:9]=[C:10]([C:11]([C:38]2[C:34]3[CH:33]=[CH:32][C:31]([O:30][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:42][C:35]=3[S:36][C:37]=2[N:39]([CH3:41])[CH3:40])=[O:13])[CH:14]=[CH:15][C:16]=1[CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)([O-:7])=[O:6]
Reactant: O=C(O)c1ccc(CN2CCCC2)c([N+](=O)[O-])c1
Reactant: CN(C)c1cc2ccc(OCc3ccccc3)cc2s1
Solvent: O=S(Cl)Cl
Product: CN(C)c1sc2cc(OCc3ccccc3)ccc2c1C(=O)c1ccc(CN2CCCC2)c([N+](=O)[O-])c1
Yield: 70 %

Procedure:
The title compound was prepared in 70% yield by essentially following the procedures outlined in Example 39, Part B (except using thionyl chloride instead of oxalyl chloride) from 3-nitro-4-[(1-pyrrolidinyl)methyl]benzoic acid (Part C, above) and 6-benzyloxy-2-(dimethylamino)benzo[b]thiophene (Example 81, Part B).
Reaction SMILES: [C:1]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[CH2:29]Cl.O>CN(C=O)C>[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[CH2:29][N:8]([C:1]([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]
Reactant: ClCc1ccncc1Br
Reactant: CC(C)(C)OC(=O)NC(=O)OC(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N(Cc1ccncc1Br)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.3 %

Procedure:
To a solution of 1.73 g of di-tert-butyl imidodicarbonate in DMF 16 ml was added 894 mg of potassium tert-butoxide under ice-cooling, followed by stirring at room temperature for 1 hour. To the reaction mixture was added a solution of 1.37 g of 3-bromo-4-(chloromethyl)pyridine in 3 ml of DMF under ice-cooling, followed by stirring at room temperature for 2 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 2.32 g of di-tert-butyl [(3-bromopyridin-4-yl)methyl]imidodicarbonate.
Reaction SMILES: Cl.Cl.Cl.Cl.[CH3:5][N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][C@H:13]([C:15]([N:17]2[CH2:22][CH2:21][N:20]([CH:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH2:19][CH2:18]2)=[O:16])[NH2:14])[CH2:8][CH2:7]1.[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([C:40](O)=[O:41])=[CH:34]2>>[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([C:40]([NH:14][C@@H:13]([C:15]([N:17]1[CH2:18][CH2:19][N:20]([CH:23]3[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]3)[CH2:21][CH2:22]1)=[O:16])[CH2:12][CH:9]1[CH2:10][CH2:11][N:6]([CH3:5])[CH2:7][CH2:8]1)=[O:41])=[CH:34]2
Reactant: CN1CCC(C[C@@H](N)C(=O)N2CCN(C3CCN(C)CC3)CC2)CC1
Reactant: O=C(O)c1cc2cc(Cl)ccc2[nH]1
Agent: Cl
Product: CN1CCC(C[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)C(=O)N2CCN(C3CCN(C)CC3)CC2)CC1

Procedure:
Using methods substantially equivalent to those described in Method D-1, the titled compound was prepared from 1-[β-(1-methylpiperidin-4-yl)-D-alanyl]-4-(1-methylpiperidin-4-yl)piperazine tetrahydrochloride and 5-chloroindole-2-carboxylic acid (46%).
Reaction SMILES: [BH4-].[Na+].[C:3]1([C:9]2[O:10][CH:11]=[C:12]([CH2:14][O:15][C:16]3[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=3)[N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CO.Cl>O>[C:3]1([C:9]2[O:10][CH:11]=[C:12]([CH2:14][O:15][C:16]3[CH:17]=[CH:18][C:19]([CH2:20][OH:21])=[CH:22][CH:23]=3)[N:13]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=Cc1ccc(OCc2coc(-c3ccccc3)n2)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: OCc1ccc(OCc2coc(-c3ccccc3)n2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91 %

Procedure:
Sodium borohydride (0.36 g) was added to a mixture of 4-(2-phenyl-4-oxazolylmethoxy)benzaldehyde (2.65 g) and methanol (50 ml) under ice-cooling, which was stirred at room temperature for 1 hour. Dilute hydrochloric acid and water were added to the reaction mixture, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated to obtain 4-(2-phenyl-4-oxazolylmethoxy)benzyl alcohol (2.43 g, yield 91%) as colorless crystals. This was recrystallized from ethyl acetate-hexane. Melting point: 141–142° C.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH2:10][O:11][CH3:12])([CH3:9])[CH3:8])[O:4][N:3]=1.[CH3:13][N:14]=[C:15]=[O:16]>CCOCC>[CH3:13][NH:14][C:15]([NH:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:9])([CH3:8])[CH2:10][O:11][CH3:12])[O:4][N:3]=1)=[O:16]
Reactant: CN=C=O
Reactant: COCC(C)(C)c1cc(N)no1
Solvent: CCOCC
Product: CNC(=O)Nc1cc(C(C)(C)COC)on1

Procedure:
A solution of 1.0 g of 3C and 1.0 g of methyl isocyanate in 15 ml of anhydrous ether was held at room temperature for 3 days. Then the solvent was evaporated and the residue was crystallized from hexane to give 1-methyl-3-(5-(1,1-dimethyl-2-methoxyethyl)-1,2-oxazol-3-yl)urea (3D), as a colorless solid, m.p.: 113°-115° C.
Reaction SMILES: [NH2:1][C:2](=O)[CH2:3][C@H:4]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:33])=CC=1.NN>O1CCCC1>[CH2:8]([O:7][C:5](=[O:6])[C@@H:4]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3][C:2](=[S:33])[NH2:1])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H](CC(N)=O)C(=O)OCc1ccccc1
Agent: NN
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](CC(N)=S)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A 1-L round bottom flask was charged with (S)-benzyl 4-amino-2-(tert-butoxycarbonylamino)-4-oxobutanoate (10.0 g, 31.0 mmol), Lawesson's reagent (6.58 g, 16.3 mmol), and tetrahydrofuran (155 mL). Hydrazine (7.8 mL, 0.248 mol) was added and the resulting mixture was stirred at room temperature for 72 h. The resulting mixture was then concentrated in vacuo and the residue purified via flash silica gel chromatography (Analogix IF-280, SF40-400 g column, gradient 90:10-60:40 Heptane:EtOAc) to yield-(S)-tert-butoxycarbonylamino-3-thiocarbamoyl-propionic acid benzyl ester. MS (ES+) 339 (M+1).
Reaction SMILES: [OH:1][C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[I:13]I>CO.S([O-])([O-])(=O)=O.[Ag+2]>[OH:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9]([I:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cccc(C)c1O
Reactant: II
Agent: [Ag+2]
Agent: O=S(=O)([O-])[O-]
Solvent: CO
Product: COC(=O)c1cc(I)cc(C)c1O
Reaction time: 3 h

Procedure:
Methyl 2-hydroxy-3-methylbenzoate (0.869 g, 5.23 mmol) in MeOH (5 mL) was added dropwise to a suspension of iodine (1.327 g, 5.23 mmol) and silver sulfate (1.63 g, 5.23 mmol), at room temperature under N2. The resultant brown suspension was stirred for 3 h after which time a colorless suspension was observed. The mixture was filtered through a plug of Celite, washed with MeOH (30 mL) and concentrated in vacuo to afford methyl 2-hydroxy-5-iodo-3-methylbenzoate, as a colorless solid. LCMS calc.=292.1; found=292.7 (M+H)+. 1H NMR (500 MHz, CHCl3): δ 11.0 (s, 1 H); 8.02 (s, 1 H); 7.62 (s, 1 H); 3.97 (s, 3 H); 2.25 (s, 3 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([NH2:8])=[NH:7].[CH:14](=[C:21]([C:24]#[N:25])[C:22]#[N:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[NH2:25][CH2:24][C:21]1[C:22]([NH2:23])=[N:7][C:6]([C:5]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:8][C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: N#CC(C#N)=Cc1ccccc1
Reactant: COc1ccc(C(=N)N)cc1OC
Product: COc1ccc(-c2nc(N)c(CN)c(-c3ccccc3)n2)cc1OC

Procedure:
The title compound, MS: m/e=336.8 (M+H+), was prepared from 3,4-dimethoxybenzamidine and 2-benzylidene-malononitrile in analogy to the process described in Example 11 as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][C:10]([C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:11]([OH:14])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[C:23](OC(=O)C)(=[O:25])[CH3:24]>>[CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][C:10]([C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:11]([O:14][C:23](=[O:25])[CH3:24])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4]
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)C1CCc2cc(C(=O)c3ccccc3)c(O)cc21
Product: COC(=O)C1CCc2cc(C(=O)c3ccccc3)c(OC(C)=O)cc21

Procedure:
A solution of 10 g of 5-benzoyl-6-hydroxy-indane-1-carboxylic acid methyl ester in 100 ml of acetic anhydride is heated to the reflux temperature for 4 hours under anhydrous conditions. It is then evaporated to dryness in vacuo. The evaporation residue is mixed with 200 ml of toluene and evaporated in vacuo. Distillation of the evaporation residue in a high vacuum gives, in the fraction boiling at 195°-200° C./0.06 mm Hg, 5-benzoyl-6-acetoxy-indane-1-carboxylic acid methyl ester in the form of a colourless oil.
Reaction SMILES: C([Li])CCC.[NH:6]1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11].[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>CCCCCC.O1CCCC1>[CH3:12][S:13][C:14]1[CH:15]=[CH:16][C:17]([S:20]([N:6]2[CH2:10][CH2:9][CH2:8][C:7]2=[O:11])(=[O:22])=[O:21])=[CH:18][CH:19]=1
Reactant: O=C1CCCN1
Reactant: CSc1ccc(S(=O)(=O)Cl)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CSc1ccc(S(=O)(=O)N2CCCC2=O)cc1
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 52 %

Procedure:
16.95 cm3 of a 1.6M solution of n-butyllithium in n-hexane is added drop by drop to 2.29 g of 2-pyrrolidinone in solution in 160 cm3 of anhydrous tetrahydrofuran cooled to -30° C., maintaining the temperature at -30° C. After agitation for 30 minutes, the mixture is poured drop by drop into a solution containing 6 g of 4-methylthio-benzenesulphonyl chloride [J. Chem. Soc. (1948) 604] in 10 cm3 of tetrahydrofuran, operating between -30° and -25° C. The whole is left to return to ambient temperature. The solvent is evaporated off under reduced pressure, the residue is taken up in water and the solid is filtered off. After crystallization from isopropanol, 3.80 g of expected product is obtained.
Reaction SMILES: [CH:1]1([C:7]2[S:11][C:10]([N:12]3[CH:17]([OH:18])[CH2:16][CH2:15][N:14]([CH3:19])[C:13]3=[O:20])=[N:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1C=CC=CC=1>[CH:1]1([C:7]2[S:11][C:10]([N:12]3[CH:17]([O:18][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:16][CH2:15][N:14]([CH3:19])[C:13]3=[O:20])=[N:9][N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(Cl)c1ccccc1
Reactant: CN1CCC(O)N(c2nnc(C3CCCCC3)s2)C1=O
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CN1CCC(OC(=O)c2ccccc2)N(c2nnc(C3CCCCC3)s2)C1=O

Procedure:
Tetrahydro-1-(5-cyclohexyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole), triethylamine (0.06 mole) and benzene (50 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. Benzoyl chloride (0.05 mole) is then added dropwise with stirring. After the addition is completed, the reaction mixture is heated at reflux with continued stirring for a period of about 30 minutes. After this time the reaction is filtered and the filtrate is stripped of solvent under reduced pressure to yield a solid residue. The residue is recrystallized to yield the desired product tetrahydro-1-(5-cyclohexyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-benzoyloxy-2(1H)-pyrimidinone.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]([CH:20]=[CH:21][CH:22]=1)[C:9]([NH:11][C:12]1[S:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][N:16]=1)=[O:10])([O-:5])=[O:4].I[CH2:24][C:25]([NH2:27])=[O:26]>CN(C)C=O>[N+:3]([C:6]1[CH:7]=[C:8]([CH:20]=[CH:21][CH:22]=1)[C:9]([N:11]=[C:12]1[N:16]([CH2:24][C:25]([NH2:27])=[O:26])[CH:15]=[C:14]([N+:17]([O-:19])=[O:18])[S:13]1)=[O:10])([O-:5])=[O:4]
Reactant: O=C(Nc1ncc([N+](=O)[O-])s1)c1cccc([N+](=O)[O-])c1
Reactant: NC(=O)CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: NC(=O)Cn1cc([N+](=O)[O-])sc1=NC(=O)c1cccc([N+](=O)[O-])c1

Procedure:
By following the procedure of Example 5, but using a dispersion of sodium hydride (2.1 g 60% w/w) in mineral oil, 3-nitro-N-(5-nitro-2-thiazolyl)benzamide (11.8 g), N,N-dimethylformamide (100 ml) and 2-iodoacetamide (11.1 g), there was obtained 2-[(3-nitrobenzoyl)imino]-5-nitro-4-thiazoline-3-acetamide, m.pt 251°-252°, after recrystallization from pyridine.