Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SH:1][CH2:2][CH:3]([CH2:24][SH:25])[C:4]([N:6]([CH:11]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[CH2:13][CH2:12]1)[CH2:7][C:8]([OH:10])=[O:9])=[O:5].II.O>C(O)C>[CH3:23][O:22][C:16]1[CH:15]=[C:14]2[C:19](=[CH:18][C:17]=1[O:20][CH3:21])[CH:11]([N:6]([C:4]([CH:3]1[CH2:24][S:25][S:1][CH2:2]1)=[O:5])[CH2:7][C:8]([OH:10])=[O:9])[CH2:12][CH2:13]2
Reactant: COc1cc2c(cc1OC)C(N(CC(=O)O)C(=O)C(CS)CS)CC2
Agent: II
Solvent: CCO
Solvent: O
Product: COc1cc2c(cc1OC)C(N(CC(=O)O)C(=O)C1CSSC1)CC2
Yield: 30.2 %

Procedure:
N-(3-Mercapto-2-mercaptomethylpropionyl)-N-(5,6-dimethoxy-1-indanyl)glycine (1 g) is dissolved in 20 ml of ethanol, and a 5% iodine solution in ethanol is added dropwise with ice cooling and stirring. When the color of iodine does not fade any more, the dropping is discontinued, the reaction mixture is poured into 100 ml of water and extracted with ethyl acetate, the extract is dried, and the solvent is then distilled off under reduced pressure. The residue is dissolved in ether, the insoluble substance is filtered off with a small amount of activated carbon, and ether is distilled off at room temperature under reduced pressure, to give 0.3 g of N-(5,6-dimethoxy-1-indanyl)-N-(1,2-dithiolane-4-carbonyl)glycine as a pale yellow viscous oil.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[NH:6][N:7]=[C:8]([OH:10])[CH:9]=1)=[O:4].[CH3:11][C:12]1[O:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13]=1[CH2:23]O.[C:25]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH3:25])[N:7]=[C:8]([O:10][CH2:23][C:13]2[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][O:16][C:12]=2[CH3:11])[CH:9]=1)=[O:4]
Reactant: COC(=O)c1cc(O)n[nH]1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Cc1onc(-c2ccccc2)c1CO
Agent: CCOC(=O)N=NC(=O)OCC
Solvent: C1CCOC1
Product: COC(=O)c1cc(OCc2c(-c3ccccc3)noc2C)nn1C
Temperature: 25 °C
Yield: 30.5 %

Procedure:
To a stirred solution of 5-hydroxy-2H-pyrazole-3-carboxylic acid methyl ester (200 mg, 1.28 mmol) and (5-methyl-3-phenyl-4-isoxazolyl)methanol (260 mg, 1.37 mmol) in THF (10 mL) at 5° C. under argon was added triphenylphosphine (437 mg, 1.67 mmol), then diethyl azodicarboxylate (290 mg, 1.67 mmol) was added dropwise. The reaction mixture was warmed to room temperature for 3 h. The reaction mixture was then evaporated and purification by chromatography (silica, heptane:ethyl acetate=1:1 to 6.5:3.5) afforded the title compound (128 mg, 31%) as a colorless oil. MS: m/e=328.3 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:3]2[C:15]3[CH2:16][CH2:17][CH2:18][CH2:19][C:14]=3[S:13][C:4]=2[N:5]=[C:6]([CH2:8][O:9][C:10](=[O:12])[CH3:11])[N:7]=1.Cl.[CH:21]1([CH2:24][NH2:25])[CH2:23]C1.[CH2:26](N(CC)CC)C>C(#N)C>[CH:24]1([N:25]([CH3:26])[C:2]2[C:3]3[C:15]4[CH2:16][CH2:17][CH2:18][CH2:19][C:14]=4[S:13][C:4]=3[N:5]=[C:6]([CH2:8][O:9][C:10](=[O:12])[CH3:11])[N:7]=2)[CH2:21][CH2:23]1
Reactant: CC(=O)OCc1nc(Cl)c2c3c(sc2n1)CCCC3
Reactant: NCC1CC1
Reactant: CCN(CC)CC
Agent: Cl
Solvent: CC#N
Product: CC(=O)OCc1nc(N(C)C2CC2)c2c3c(sc2n1)CCCC3
Temperature: 25 °C
Reaction time: 12 h
Yield: 96 %

Procedure:
A mixture of acetic acid 4-chloro-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-ylmethyl ester (3.5 g, 0.011 mol), cyclopropylmethylamine hydrochloride (2.5 g, 0.023 mol) and triethylamine (4.6 g, 0.046 mol) in acetonitrile (15 ml) was stirred at room temperature for 12 h. The solvent was removed by distillation, and the residue was diluted with water and extracted with ethyl acetate (3×25 ml). The combined organic layers were dried over anhydrous sodium sulphate, concentrated to give acetic acid 4-(cyclopropyl-methyl-amino)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-ylmethyl ester (3.5 g, 89%) as brown solid. 1H NMR (400 MHz, CDCl3): δ 0.43-0.47 (m, 2H), 0.69-0.77 (m, 2H), 1.71-1.77 (m, 2H), 1.87-1.93 (m, 2H), 2.18 (s, 3H), 2.82-2.92 (m, 5H), 3.03 (s, 3H), 5.19 (s, 2H); LC-MS: [M+H]=331.8 m/z.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])(=O)=O.[CH2:21]([NH2:23])[CH3:22]>C1COCC1>[CH2:21]([NH:23][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11](=[O:12])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:22]
Reactant: CCN
Reactant: CS(=O)(=O)OCCCCNC(=O)OCc1ccccc1
Solvent: C1CCOC1
Product: CCNCCCCNC(=O)OCc1ccccc1

Procedure:
Following the general procedure of Example 4, Step 2, and making non-critical variations but using 4-(benzyloxycarbonylamino)butyl methanesulfonate and ethyl amine in THF, the compound of Step 1 was obtained.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([C:14]2[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16]([OH:18])=O)=[O:13])=[C:4]1[CH3:23])[CH3:2].[NH:24]([C:31]1[CH:40]=[CH:39][CH:38]=[CH:37][C:32]=1[C:33]([O:35][CH3:36])=[O:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2([N:24]([C:31]3[CH:40]=[CH:39][CH:38]=[CH:37][C:32]=3[C:33]([O:35][CH3:36])=[O:34])[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:14]3[C:15](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:16](=[O:18])[O:13]2)=[C:4]1[CH3:23])[CH3:2]
Reactant: COC(=O)c1ccccc1Nc1ccccc1
Reactant: CCn1c(C)c(C(=O)c2ccccc2C(=O)O)c2ccccc21
Product: CCn1c(C)c(C2(N(c3ccccc3)c3ccccc3C(=O)OC)OC(=O)c3ccccc32)c2ccccc21
Yield: 7.7 %

Procedure:
Following a procedure similar to that described in Example 1A but employing 3.1 g of 2-(1-ethyl-2-methyl-3-indolylcarbonyl)benzoic acid and 2.3 g of methyl 2-anilinobenzoate there was obtained 0.4 g of 3-(1-ethyl-2-methyl-3-indolyl)-3-[N-(2-methoxycarbonylphenyl)-N-phenylamino]phthalide, m.p. 80°-115° C. A toluene solution of the product contacted with acidic clay or phenolic resin developed a pink-colored image.
Reaction SMILES: [CH:1]1([C@H:7]([NH:37][C:38]([C:40]2[CH:45]=[N:44][CH:43]=[CH:42][N:41]=2)=[O:39])[C:8]([NH:10][C@@H:11]([C:33]([CH3:36])([CH3:35])[CH3:34])[C:12]([N:14]([C@H:16]2[CH2:20][N:19]([C:21](=[O:29])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:18][C@H:17]2[C:30]([OH:32])=O)[CH3:15])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[NH2:65][CH:66]([CH2:75][CH2:76][CH3:77])[CH:67]([OH:74])[C:68]([NH:70][CH:71]1[CH2:73][CH2:72]1)=[O:69]>ClCCl.CCOC(C)=O>[CH:1]1([C@H:7]([NH:37][C:38]([C:40]2[CH:45]=[N:44][CH:43]=[CH:42][N:41]=2)=[O:39])[C:8]([NH:10][C@@H:11]([C:33]([CH3:36])([CH3:35])[CH3:34])[C:12]([N:14]([C@H:16]2[CH2:20][N:19]([C:21]([NH:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:29])[CH2:18][C@H:17]2[C:30]([NH:65][C@@H:66]([CH2:75][CH2:76][CH3:77])[CH:67]([OH:74])[C:68]([NH:70][CH:71]2[CH2:72][CH2:73]2)=[O:69])=[O:32])[CH3:15])=[O:13])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CN(C(=O)[C@@H](NC(=O)[C@@H](NC(=O)c1cnccn1)C1CCCCC1)C(C)(C)C)[C@H]1CN(C(=O)Nc2ccccc2)C[C@H]1C(=O)O
Reactant: CCCC(N)C(O)C(=O)NC1CC1
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCC[C@H](NC(=O)[C@@H]1CN(C(=O)Nc2ccccc2)C[C@@H]1N(C)C(=O)[C@@H](NC(=O)[C@@H](NC(=O)c1cnccn1)C1CCCCC1)C(C)(C)C)C(O)C(=O)NC1CC1
Reaction time: 3 h
Yield: 49 %

Procedure:
A mixture of the product from Example 48, Part A (50 mg, 0.08 mmol), N-(3-dimethyl aminopropyl)-N′-ethylcarbodiimide hydrochloride (17 mg, 0.09 mmol), 1-hydroxybenzotriazole (12 mg, 0.09 mmol), Hunig's base (42 uL, 0.24 mmol) and 3-amino-N-cyclopropyl-2-hydroxyhexanamide (WO2002018369-A2; Example 119, cpd xiii′) (15 mg, 0.08 mmol)) in dichloromethane (5 mL) was stirred for 3 hours and diluted with 100 mL EtOAc, washed with 10 mL 1 M H3PO4, 10 mL 10% NaHCO3, 20 mL with brine, dried (MgSO4), and concentrated to give the title compound (31 mg, 49%). MS (ESI+) m/z=790.7 (M+H)+.
Reaction SMILES: [C:1]1([P:7](Cl)Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]([OH:12])[CH3:11].N1C=CC=CC=1.[OH2:19]>CCOCC>[C:1]1([PH:7](=[O:19])[O:12][CH2:10][CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCO
Reactant: ClP(Cl)c1ccccc1
Reactant: O
Solvent: CCOCC
Solvent: c1ccncc1
Product: CCO[PH](=O)c1ccccc1
Reaction time: 1 h

Procedure:
A solution of phenylphosphonous dichloride (66 g, 0.37 mol) in dry ether (100 mL) was treated dropwise with a solution of ethanol (21.6 mL, 0.37 mol) and pyridine (29.6 mL, 0.37 mol) in ether (200 mL) at room tempeature under argon. After stirring for one hour, a mixture of water (6.6 mL, 0.37 mol) and pyridine (29.6 mL) was added slowly. The reaction mixture was filtered, washed with ether, and the ether evaporated to give an oil. The oil was distilled in the Kugelrohr and then through a short Vigreux column at 95°-98° C. (0.05 mmHg); lit. (T. L. Emmick et al., J. Am. Chem. Soc., 1968, 90, 3459) 102°-103° C. (0.2 mmHg). Yield 44.3 g (70%). 1H NMR (CDCl3)δ 7.57 (d, J=569 Hz, 1H), 8.0-7.4 (m, 5H), 4.13 (2 q, JH-H =7 Hz, JP-H =14 Hz, 2H), 1.35 (t, J=7 Hz, 3H).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[OH:14].C(N(CC)CC)C>C(Cl)Cl>[CH3:1][S:2]([O:14][C:8]1[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=1[NH2:6])(=[O:4])=[O:3]
Reactant: Nc1cc(Cl)ccc1O
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Oc1ccc(Cl)cc1N
Temperature: 25 °C
Reaction time: 18 h

Procedure:
174.5 g (1.52 mol) of methanesulfonyl chloride were added dropwise at 10°-15° C. to a solution of 218.7 g (1.52 mol) of 2-amino-4-chlorophenol and 153.8 g (1.52 mol) of triethylamine in 400 ml of methylene chloride. The mixture was stirred for 18 hours at 25° C. and was introduced into ice water, and the organic phase was separated off, washed twice with water and dried over Na2SO4. After the solvent had been distilled off, a gradually crystallizing residue of the product remained, which was sufficiently pure for further reaction (329.5 g, 98% of theory). The product could be recrystallized from methanol/water (mp. 70°-71° C.).
Reaction SMILES: [C:1]1(=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ClC1C=CC=[C:12]([C:16]([O:18]O)=O)C=1.[CH:20](Cl)(Cl)Cl>>[CH:1]1([CH2:20][C:16](=[O:18])[CH3:12])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C1CCCCCC1
Reactant: ClC(Cl)Cl
Product: CC(=O)CC1CCCCCC1
Temperature: 25 °C
Reaction time: 36 h

Procedure:
A solution of cycloheptanone (5 gms, 44 mmol) in chloroform (100 ml) was added to a solution of m-chloroperbenzoic acid (12.3 gms, 79.3 mmol) in chloroform (75 ml) and stirred at rt for 36 hrs. The reaction mixture was filtered and the filtrate washed with aq Na2CO3 solution (5%, 3×50 ml) until pH aq layer was at 8-9. Organic layer was washed with water and brine and dried over Na2SO4. The insolubles wer filtered off and the organic layer was concentrated under vacuum to give the lactone (20) (3.5 gms) as waxy solid.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:13][O:14][C:15]1[CH:59]=[C:58]([O:60][CH3:61])[CH:57]=[C:56]([O:62][CH3:63])[C:16]=1[CH:17]=[CH:18][CH:19]([S:29]([CH:32]([CH:42]=[CH:43][C:44]1[C:49]([O:50][CH3:51])=[CH:48][C:47]([O:52][CH3:53])=[CH:46][C:45]=1[O:54][CH3:55])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[C:35]([NH2:41])[CH:34]=1)(=[O:31])=[O:30])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([NH2:28])[CH:21]=1>O1CCCC1>[CH3:63][O:62][C:56]1[CH:57]=[C:58]([O:60][CH3:61])[CH:59]=[C:15]([O:14][CH3:13])[C:16]=1/[CH:17]=[CH:18]/[CH:19]([S:29]([CH:32](/[CH:42]=[CH:43]/[C:44]1[C:45]([O:54][CH3:55])=[CH:46][C:47]([O:52][CH3:53])=[CH:48][C:49]=1[O:50][CH3:51])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[C:35]([NH:41][C:8](=[O:9])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH:34]=1)(=[O:31])=[O:30])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([NH:28][C:8](=[O:9])[C:7]2[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH:21]=1
Reactant: COc1cc(OC)c(C=CC(c2ccc(OC)c(N)c2)S(=O)(=O)C(C=Cc2c(OC)cc(OC)cc2OC)c2ccc(OC)c(N)c2)c(OC)c1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: C1CCOC1
Product: COc1cc(OC)c(/C=C/C(c2ccc(OC)c(NC(=O)c3ccc([N+](=O)[O-])cc3)c2)S(=O)(=O)C(/C=C/c2c(OC)cc(OC)cc2OC)c2ccc(OC)c(NC(=O)c3ccc([N+](=O)[O-])cc3)c2)c(OC)c1
Reaction time: 8 h
Yield: 72 %

Procedure:
To a solution of 4-nitrobenzoyl chloride (10 mmol) in tetrahydrofuran (40 mL) was added dropwise a solution of 2,4,6-trimethoxystyryl-3-amino-4-methoxy-benzylsulfone (10 mmol) in tetrahydrofuran. The solution was stirred overnight and the completion of the reaction was monitored by TLC. The solvent was removed and the residue was taken in dichloromethane and washed with water. The organic layer was dried over anhydrous sodium sulfate and evaporated to give (E)-2,4,6-trimethoxystyryl-3-(4-nitrobenzamido)-4-methoxybenzylsulfone in 72% yield. m.p. 206-208° C. NMR (DMSO-d6) δ 3.80 (s, 3H), 3.81 (s, 6H), 3.83 (s, 3H), 4.18 (s, 2H), 6.08 (s, 2H), 7.14-7.23 (d, 1H vinylic), 6.97-7.86 (m, aromatic), 9.05 (s, 1H).
Reaction SMILES: S(Cl)(Cl)=O.[I:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[OH:15].[CH3:16]O>>[CH3:16][O:11][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][C:6]([I:5])=[C:7]([OH:15])[CH:8]=1
Reactant: O=C(O)c1ccc(I)c(O)c1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(I)c(O)c1
Temperature: 50 °C
Reaction time: 0.17 h

Procedure:
5 ml of thionyl chloride was added to 120 ml of MeOH at 0° C. The solution was stirred for 10 min and 20 g of 4-Iodo-3-hydroxy-benzoic acid was added. The reaction was stirred for 16 h at RT then heated to 50° C. for 3 h. The solvents were removed under reduced pressure. The residue was used directly in the next step. Yield 21 g.
Reaction SMILES: [C:1]1([NH:7][C:8](=O)[CH:9]=[CH:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19]1(C)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[S:26](Cl)(Cl)=O>CN(C=O)C.C(N(CC)CC)C>[C:1]1([N:7]=[C:8]([S:26][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:9]=[CH:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(C=COc1ccccc1)Nc1ccccc1
Reactant: O=S(Cl)Cl
Reactant: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C(=CC(=Nc1ccccc1)Sc1ccccc1)Oc1ccccc1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
N-phenyl-3-phenoxyacrylamide (1.5 g) was suspended to toluene (80 ml), then thionyl chloride (0.82 ml), triethylamine (1.8 ml) and one drop of DMF were added thereto at room temperature. The mixture was stirred on the 60° C. oil bath for three hours. Then it was cooled and filtered off the insoluble matter. The filtrate was concentrated under reduced pressure. The residue was dissolved to DMF (80 ml). Sodium salt of thiophenol (0.82 g) was added to it under ice-cooling, and stirred for 2 hours. t-Butyl methyl ether (250 ml) was added to the reaction mixture. It was successively washed with 1N aqueous sodium hydroxide solution, water and aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered off an inorganic salt, concentrated under reduced pressure. The residue was isolated and purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain phenyl N-phenyl-3-(phenoxy)thioacrylimidate (0.28 g) as yellow oil.
Reaction SMILES: C[CH:2]1[N:11]2[C:6]3[C:7](=[CH:16][CH:17]=[C:18](C4NN=NN=4)[C:5]=3[CH2:4][CH2:3]1)[C:8](=[O:15])[C:9]([C:12]([OH:14])=[O:13])=[CH:10]2.C1(N=C=O)C=CC=CC=1>O>[O:15]=[C:8]1[C:7]2=[CH:16][CH:17]=[CH:18][C:5]3=[C:6]2[N:11]([CH2:2][CH:3]=[CH:4]3)[CH:10]=[C:9]1[C:12]([OH:14])=[O:13]
Reactant: CC1CCc2c(-c3nnn[nH]3)ccc3c(=O)c(C(=O)O)cn1c23
Solvent: O
Solvent: O=C=Nc1ccccc1
Product: O=C(O)c1cn2c3c(cccc3c1=O)C=CC2
Temperature: 150 °C

Procedure:
A mixture of 1.0 g of 6,7-dihydro-5-methyl-1-oxo-8-(5-tetrazolyl)-1H,5H-benzo[ij]quinolizine-2-carboxylic acid and 5 ml (46 mmole) of phenyl isocyanate was heated at 150° C. for one hour. The mixture was then cooled and water was added. The solid was separated by filtration and recrystallized twice from aqueous N,N-dimethylformamide to provide 6,7-dihydro-5-methyl-8-[2-(5-N-anilino)-1,3,4-oxadiazolyl)]-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid solvated with N,N-dimethylformamide m.p. >300° C. Analysis: Calculated for C22H18N4O4.C3H7NO: %C, 63.1; %H, 5.3; %N, 14.7; Found: %C, 63.1; %H, 5.3; %N, 15.1.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7](Cl)=[O:8])([CH3:3])[CH3:2].[NH2:14]C1C=CC(C#N)=C(C(F)(F)F)C=1.C(N(CC)CC)C>ClCCl>[CH:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([NH2:14])=[O:8])([CH3:3])[CH3:2]
Reactant: N#Cc1ccc(N)cc1C(F)(F)F
Reactant: CC(C)Oc1ccccc1C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)Oc1ccccc1C(N)=O

Procedure:
2-Isopropoxy-benzoyl chloride was condensed with 4-Amino-2-trifluromethyl benzonitrile in dichloromethane in presence of triethylamine as acid scavenger to yield N-4-Cyano-3-trifluoromethyl-phenyl)-2-Isopropoxy-benzamide. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product.
Reaction SMILES: Cl.Cl[C:3]([C:5]1[CH:6]=[CH:7][N:8]2[C:12]=1[CH2:11][S:10][CH:9]2[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[O:4].[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][CH:32]=1)[NH2:29].C(N(CC)CC)C.C>O1CCOCC1.C(#N)C>[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][C:26]1[CH:27]=[C:28]([NH:29][C:3]([C:5]2[CH:6]=[CH:7][N:8]3[C:12]=2[CH2:11][S:10][CH:9]3[C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[O:4])[CH:30]=[CH:31][CH:32]=1
Reactant: Nc1cccc(Oc2ccccn2)c1
Reactant: O=C(Cl)c1ccn2c1CSC2c1cccnc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: CC#N
Product: O=C(Nc1cccc(Oc2ccccn2)c1)c1ccn2c1CSC2c1cccnc1
Temperature: 60 °C
Reaction time: 7 h
Yield: 51.6 %

Procedure:
7-Chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (12 g) is added, at a temperature between 60° and 68° C., to a solution of 3-(2-pyridyloxy)aniline (7.4 g) and triethylamine (8.1 g) in dioxane (200 cc) which is heated to a temperature in the vicinity of 60° C., in the course of 5 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 7 hours and then stirred at a temperature in the vicinity of 20° C. for 16 hours. The solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. The residue is dissolved in methylene chloride (300 cc). The solution obtained is washed twice with distilled water (500 cc in total), twice with an aqueous 1N sodium hydroxide solution (300 cc in total) and twice with distilled water (500 cc in total) and then dried over anhydrous magnesium sulphate, treated with decolourizing charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. A crude product (15.8 g) is thereby obtained, which is dissolved in boiling acetonitrile (100 cc). Decolourizing charcoal (0.5 g) is added to the solution obtained and the suspension is filtered in the heated state. The filtrate is cooled at a temperature in the vicinity of 20° C. for 3 hours. The crystals formed are separated by filtration, washed 3 times with acetonitrile (45 cc in total) and 3 times with diethyl ether (90 cc in total) and then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets. N-[3-(2-pyridyloxy)phenyl]-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (8.5 g) in the form of cream-coloured crystals, m.p. 132° C., is thereby obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:20](=[CH:24][N:25]([CH2:27][CH2:28][CH2:29]O)[N:26]=3)[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH3:31][S:32]([CH2:35][CH2:36][NH:37][S:38]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[N+:47]([O-:49])=[O:48])(=[O:40])=[O:39])(=[O:34])=[O:33].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:20](=[CH:24][N:25]([CH2:27][CH2:28][CH2:29][N:37]([CH2:36][CH2:35][S:32]([CH3:31])(=[O:33])=[O:34])[S:38]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[N+:47]([O-:49])=[O:48])(=[O:39])=[O:40])[N:26]=3)[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1
Reactant: CS(=O)(=O)CCNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: OCCCn1cc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2n1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CS(=O)(=O)CCN(CCCn1cc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2n1)S(=O)(=O)c1ccccc1[N+](=O)[O-]

Procedure:
A solution of 3-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]propanol (50 mg), N-[2-(methylsulfonyl)ethyl]-2-nitrobenzenesulfonamide (47 mg), 1,1′-(azodicarbonyl)dipiperidine (59 mg) and tributylphosphine (47 mg) in tetrahydrofuran (2 mL) was stirred at room temperature for 4 hrs. After the completion of the reaction, water was added to the reaction mixture and the mixture was diluted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol=4/1→1/4) to give N-{3-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]propyl}-N-[2-(methylsulfonyl)ethyl]-2-nitrobenzenesulfonamide. To a solution of this compound in tetrahydrofuran (2 mL) were added 2-mercaptoethanol (12 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 mg), and the mixture was stirred at room temperature for 3 hrs. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=10/1) to give the title compound (34 mg) as a white solid.
Reaction SMILES: [C:1]1([SiH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:14]1[CH:16]([CH2:17][CH2:18][CH:19]=[CH2:20])[CH2:15]1>C1(C)C=CC=CC=1.C(O)C.O.[Rh](Cl)(Cl)Cl>[C:8]1([Si:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[O:14][CH2:15]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[O:14][CH2:15]2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: c1ccc([SiH2]c2ccccc2)cc1
Reactant: C=CCCC1CO1
Agent: Cl[Rh](Cl)Cl
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCO
Product: c1ccc([Si](CCCCC2CO2)(CCCCC2CO2)c2ccccc2)cc1
Yield: 78.8 %

Procedure:
27.6 g of diphenylsilane (0.15 mole) were dispersed in 100 g toluene with 0.02 g rhodiumtrichloride hydrate (as a solution in 0.5 cc ethanol) then the solution was brought to 100° C. when 32 g 1,2-epoxy-5-hexene (0.32 mole) were added dropwise. A two hour hold at 100°-110° followed, which consumed all SiH per IR analysis. Solvent was distilled off leaving 45 g residue as a mobile, 15 cstk viscosity fluid product, nD25 =1.5532. Infrared analysis was consistent with the proposed structure, with evidence of siloxane by products also present.