Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CCCC)CCCC)CCC.[C:48]([OH:52])(=[O:51])[CH:49]=[CH2:50]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:12][C:9]1[CH:10]=[CH:11][C:2]([C:49](=[CH2:50])[C:48]([OH:52])=[O:51])=[C:3]([C:4]([O:6][CH3:7])=[O:5])[CH:8]=1
Reactant: C=CC(=O)O
Reactant: COC(=O)c1cc(Cl)ccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCCCN(CCCC)CCCC
Solvent: Cc1ccccc1
Product: C=C(C(=O)O)c1ccc(Cl)cc1C(=O)OC
Temperature: 110 °C
Yield: 65.8 %

Procedure:
To a solution of methyl 2-bromo-5-chlorobenzoate (6.30 g), tri-o-tolylphosphine (P(o-tol)3) (770 mg), tri-n-butylamine (9.38 g) and acrylic acid (3.64 g) in toluene (20 mL) was added palladium acetate (284 mg) under nitrogen atmosphere, and the mixture was heated at 110° C. for 3 hours. The mixture was washed with 1N HCl, dried, filtered, and concentrated. The residue was purified by silica gel column chromatography, and the fractions containing the desired compound were combined, dissolved in ethyl acetate, and extracted with a saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was acidified with hydrochloric acid, extracted with ethyl acetate, and the organic layer was dried, filtered, and concentrated to give 2-(4-chloro-2-methoxycarbonylphenyl)acrylic acid (4.0 g, 66%).
Reaction SMILES: [Cl:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([Br:11])[C:8]([Br:12])=[CH:7][C:5]=2[N:6]=1.C[Si](/N=C(/O[Si](C)(C)C)\C(F)(F)F)(C)C.C(O[C@@H:32]1[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]1[O:34][C:35](=[O:37])[CH3:36])(=O)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>CC#N.CCOC(C)=O>[Cl:1][C:2]1[N:3]([C@@H:32]2[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]2[O:34][C:35](=[O:37])[CH3:36])[C:4]2[CH:10]=[C:9]([Br:11])[C:8]([Br:12])=[CH:7][C:5]=2[N:6]=1
Reactant: Clc1nc2cc(Br)c(Br)cc2[nH]1
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: C[Si](C)(C)/N=C(/O[Si](C)(C)C)C(F)(F)F
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@@H](n2c(Cl)nc3cc(Br)c(Br)cc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.5 %

Procedure:
A suspension of 931 mg (3 mmole) of 2-chloro-5,6-dibromobenzimidazole (17) in 15 ml of dry CH3CN was treated with 0.8 mL (3 mmole) of N,O-bis(trimethylsilyl)trifluroacetamide (BSTFA) at 75° C. for 10 min to give a clear solution. To this solution, was added 955 mg (3 mmole) of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and 0 64 mL (3.3 mmole) of trimethylsilyl triflate (TMSTf). Stirring was continued at 75° C. for 1 hr. The reaction mixture was cooled to room temperature and then diluted with 100 mL of EtOAc. The EtOAc solution was washed with a sat. NaHCO3 solution (100 mL×2), sat. NaCl solution (100 mL), dried (Na2SO4), and evaporated. The residue was chromatographed on a silica column (3×20 cm, eluted with CHCl3). Evaporation of fractions 4-10 and recrystallization of the residue from MeOH gave 946 mg (56%) of 56 as white crystals. mp 140°-142° C.; MS m/e 565.9082 (0.9%, M+ =565.9091); 1H NMR (DMSO-d6) d 8.20 (s, 1,7-H), 8.11 (s, 1, 4-H), 6.25 (d, 1, 1'-H), 5.55 (t, 1, 2'-H), 5.43 (dd, 1, 3'-H), 4.47 (m, 2, 5'-H, 4'-H), 4.37 (m, 1, 5"-H), 2.15, 2.14, 2.02 (3×s, 3×, 3.3×Ac). Evaporation of fractions 13-15 gave 392 mg (23%) of the a anomer as a white foam. 1H NMR (DMSO-d6) d 8.07, 8.06 (2×s, 2, 4-H, 7-H), 6.70 (d, 1, 1'-H), 5.71 (t, 1, 2'-H), 5.50 (dd, 1, 3'-H), 4.81 (m, 1, 4'-H), 4.36 (dd, 1, 5'-H), 427 (dd, 1, 5"-H).
Reaction SMILES: CO[C:3]([C:5]1[CH:9]=[CH:8][S:7][C:6]=1[NH2:10])=[O:4].[O-:11][C:12]#[N:13].[K+]>C(O)(=O)C.O>[NH:10]1[C:6]2[S:7][CH:8]=[CH:9][C:5]=2[C:3](=[O:4])[NH:13][C:12]1=[O:11]
Reactant: N#C[O-]
Reactant: COC(=O)c1ccsc1N
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: O=c1[nH]c(=O)c2ccsc2[nH]1
Temperature: 25 °C
Reaction time: 15 h
Yield: 25.2 %

Procedure:
To a stirred solution of methyl-2-aminothiophene-3-carboxylate (2.03 g, 12.9 mmol) in acetic acid (65 mL) and water (6.5 mL) was added a solution of potassium cyanate (3.14 g, 38.7 mmol) dissolved in water (10.4 mL) dropwise via syringe. The reaction was stirred at room temperature for 15 h, upon completion of the reaction; the reaction mixture was concentrated to 75% and filtered off white solid. To the solid was added 6% aqueous sodium hydroxide (16 mL) and refluxed for 2 h. After cooling to room temperature, the solution was acidified using 12N HCl to pH=6. The resultant precipitate was filtered, washed with water and dried in a vacuum oven overnight to give 546 mg (25%) of the title compound as an orange-solid which was used without any further purification:
Reaction SMILES: C(Cl)Cl.[F:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([NH2:26])=[C:19]2[N:18]=1.CCN(C(C)C)C(C)C.Cl[C:37](=[O:42])[C:38]([O:40][CH3:41])=[O:39]>>[F:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([NH:26][C:37](=[O:42])[C:38]([O:40][CH3:41])=[O:39])=[C:19]2[N:18]=1
Reactant: COC(=O)C(=O)Cl
Reactant: Nc1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)C(=O)Nc1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 84.9 %

Procedure:
A DCM (5 mL, 0.7928 mmol) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 250 mg, 0.7928 mmol) and DIEA (0.2071 mL, 1.189 mmol) was first cooled in an ice-water bath, then methyl 2-chloro-2-oxoacetate (0.07657 mL, 0.8325 mmol) was added to reaction drop-wise. Ice bath was removed and the reaction was stirred at ambient temperature for approx. 10 minutes to reach completion. The reaction was washed with 10% citric acid (aqueous). The aqueous layer was back-washed with DCM. The combined organic layer was washed with 1:1 water/brine, dried (Na2SO4) and concentrated. The crude oil residue was directly purified by silica chromatography, eluting with EtOAc/hexanes 1:1 to 2:1, yielding the final product as a pale-yellowish foamy powder (270 mg, 85% yield). MS (apci) m/z=402.2 (M+H).
Reaction SMILES: CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:15]=[C:16]([S:20]([N:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=2)[N:8]=1)=O.[F:27][C:28]1[CH:29]=[C:30]([NH:34][NH2:35])[CH:31]=[CH:32][CH:33]=1>>[F:27][C:28]1[CH:29]=[C:30]([N:34]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:15]=[C:16]([S:20]([N:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=4)[N:8]=3)=[CH:4][CH:3]=[N:35]2)[CH:31]=[CH:32][CH:33]=1
Reactant: NNc1cccc(F)c1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(S(=O)(=O)N(C)C)c2)ccc1=O
Product: CN(C)S(=O)(=O)c1cccc(-n2ccc(=O)c(-c3ccnn3-c3cccc(F)c3)n2)c1

Procedure:
The product was obtained starting from 3-[3-((E)-3-Dimethylamino-acryloyl)-4-oxo-4H-pyridazin-1-yl]-N,N-dimethyl-benzenesulfonamide (A-12) and 3-fluoro-phenylhydrazine according to the method described for example 91. MS: M=440.2 (M+H)+
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:14])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([Br:12])=[CH:7][C:6]=2[Cl:13].[CH3:15][C:16]([Si:19](Cl)([CH3:21])[CH3:20])([CH3:18])[CH3:17]>>[C:16]([Si:19]([O:14][C:3]1[C:2]([Br:1])=[CH:11][C:10]2[C:5](=[C:6]([Cl:13])[CH:7]=[C:8]([Br:12])[CH:9]=2)[CH:4]=1)([CH3:21])[CH3:20])([CH3:18])([CH3:17])[CH3:15]
Reactant: Oc1cc2c(Cl)cc(Br)cc2cc1Br
Reactant: CC(C)(C)[Si](C)(C)Cl
Product: CC(C)(C)[Si](C)(C)Oc1cc2c(Cl)cc(Br)cc2cc1Br

Procedure:
The title compound was prepared by reacting 3,6-dibromo-8-chloro-2-naphthol (3.00 g, 8.92 mmol) with TBDMS-Cl (1.75 g, 150.7 mmol) according to method F to yield 3.36 g (84%) of a white solid: mp 58–64° C.; 1H NMR (CDCl3): δ 0.34 (6H, s), 1.08 (9H, s); 7.57 (1H, s), 7.62 (1H, d, J=1.72 Hz), 7.75 (1H, d, J=1.24 Hz), 7.97 (1H, s); MS (ESI) m/z 333/335/337 (M−H)−.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:4]=[C:5]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[CH:13]=2)[CH:6]=[CH:7][C:8]=1[CH3:9].C[Al](C)C.[CH2:28]([N:30]([C:37]1[C:45]2[C:40](=[N:41][CH:42]=[CH:43][N:44]=2)[S:39][C:38]=1[C:46]([O-])=[O:47])C(=O)C(F)(F)F)[CH3:29]>C1(C)C=CC=CC=1.CCOC(C)=O>[C:21]([C:18]([C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[C:11]([NH:10][C:5]1[CH:6]=[CH:7][C:8]([CH3:9])=[C:3]([NH:2][C:46]([C:38]2[S:39][C:40]3=[N:41][CH:42]=[CH:43][N:44]=[C:45]3[C:37]=2[NH:30][CH2:28][CH3:29])=[O:47])[CH:4]=1)=[O:23])([CH3:20])[CH3:19])#[N:22]
Reactant: CCN(C(=O)C(F)(F)F)c1c(C(=O)[O-])sc2nccnc12
Reactant: Cc1ccc(NC(=O)c2cccc(C(C)(C)C#N)c2)cc1N
Agent: C[Al](C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCNc1c(C(=O)Nc2cc(NC(=O)c3cccc(C(C)(C)C#N)c3)ccc2C)sc2nccnc12
Temperature: 25 °C
Yield: 5 %

Procedure:
To a suspension of N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (40 mg, 0.121 mmol) in toluene (1 mL) was added trimethylaluminum (0.243 mL, 0.485 mmol) and stirred for 15 at rt. 7-(N-ethyl-2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxylate 45 (42.1 mg, 0.121 mmol) in toluene (1 mL) was added and the reaction was stirred overnight at 70° C. Diluted with EtOAc and washed with seignette salt solution. Organic layer was washed with brine, dried and evaporated. Purification by HPLC gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(ethylamino)thieno[2,3-b]pyrazine-6-carboxamide 46 (3 mg, 4.96%). NMR (400 MHz, DMSO-d6) 1.20 (t, J=7.4 Hz, 3H), 1.75 (s, 6H), 2.22 (s, 1H), 3.98 (q, J=14.0 and 6.5 Hz, 12H), 7.26 (d, J=8.2 Hz, 1H), 7.58-7.64 (m, 2H), 7.75 (d, J=7.8 Hz, 1H), 7.82 (d, J=1.9 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.04-8.11 (m, 2H), 8.74 (d, J=2.3 Hz, 1H), 8.78 (d, J=2.3 Hz, 1H), 9.53 (s, 1H), 10.32 (s, 1H). (m/z)=499 (M+H)+.
Reaction SMILES: Br[CH:2]([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].C([O-])=[O:13].[Na+].O>CO>[OH:13][CH:2]([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4]
Reactant: O=C[O-]
Reactant: CC(Br)C(=O)c1ccccc1
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(O)C(=O)c1ccccc1
Yield: 62.8 %

Procedure:
To a solution of 2-bromo-1-phenylpropan-1-one (6.0 g, 28.2 mmol) in methanol (50 mL) was added sodium formate (7.66 g, 113 mmol) and the mixture was heated under reflux for 8 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4:1) to give the title compound (2.66 g, yield 63%) as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[N:6]([C:7]2[N:17]=[CH:16][CH:15]=[CH:14][C:8]=2[C:9](OCC)=[O:10])[N:5]=[N:4][N:3]=1.CN(C)C=O.[O-]CC.[K+]>C(O)(=O)C>[N:5]1[N:6]2[C:7]3[C:8]([C:9]([OH:10])=[CH:1][C:2]2=[N:3][N:4]=1)=[CH:14][CH:15]=[CH:16][N:17]=3
Reactant: CCOC(=O)c1cccnc1-n1nnnc1C
Agent: CC[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: Oc1cc2nnnn2c2ncccc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.1 %

Procedure:
Ethyl 2-(5-methyl-1H-tetrazol-1-yl)nicotinate (6.3 g, 27 mmole) was covered with N,N-dimethylformamide (50 mL), potassium ethoxide (4.5 g, 54 mmole) was added and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was poured into ice water containing about 17 mL of acetic acid. The resulting precipitate was isolated by filtration, washed with water then dried to provide 4.5 g of tetrazolo[1,5-a][1,8]naphthyridin-5-ol as an off white solid, m.p. 236° (decomposition). Analysis: Calculated for C8H5N5O: % C, 51.34; % H, 2.69; % N, 37.42; Found: % C, 51.23; % H, 2.77; % N, 37.25.
Reaction SMILES: O.[NH2:2][C:3]1[C:8]([C:9](=[S:17])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:18][C:19]([OH:21])=[O:20].[Na].[CH2:23](I)[CH3:24].O>CN(C)C=O>[NH2:2][C:3]1[C:8]([C:9](=[S:17])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:18][C:19]([O:21][CH2:23][CH3:24])=[O:20]
Reactant: CCI
Reactant: Cc1ccc(C(=S)c2cccc(CC(=O)O)c2N)cc1
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)Cc1cccc(C(=S)c2ccc(C)cc2)c1N
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
Seventeen grams (0.05 mole) of sodium 2-amino-3-(4-methylthiobenzoyl)phenylacetic acid monohydrate are dissolved in approximately 150 ml of dimethylformamide and the solution treated with 33 g ethyl iodide. The solution is stirred at room temperature for 2.5 hrs. and added to water and the mixture extracted several times with benzene. The combined benzene extracts are washed with dilute base and water, dried over sodium sulfate and concentrated to obtain the titled compound.
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15](Cl)(=O)[C:16]1[C:17]([O:22][CH3:23])=[CH:18][CH:19]=[CH:20][CH:21]=1>CN1CCCC1=O>[C:1]1([N:7]2[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:14]=[C:15]2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COc1ccccc1C(=O)Cl
Reactant: Nc1ccccc1Nc1ccccc1
Solvent: CN1CCCC1=O
Product: COc1ccccc1-c1nc2ccccc2n1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
N-phenyl-1,2-phenylenediamine (25 g, 0.136 mol) was dissolved in 100 ml N-methyl-2-pyrrolidinone (NMP) and o-anisoyl chloride (23.2 g, 0.136 mol) was then added to the solution at room temperature under nitrogen. The reaction mixture was stirred for 30 minutes at room temperature and then the temperature was increased to 220° C. for three hours during which time a white solid precipitated out of solution. After cooling, 150 ml of water was added to the reaction mixture and product was extracted with 300 ml of dichloromethane. The organic layer was washed with water and then dried with sodium sulfate. After removal of the solvents, the desired product o-(1-phenyl-2-benzimidazolyl) anisole was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10](O)=[O:11].[CH3:25][S:26]([NH2:29])(=[O:28])=[O:27].Cl>S(Cl)(Cl)=O>[Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([NH:29][S:26]([CH3:25])(=[O:28])=[O:27])=[O:11]
Reactant: O=C(O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Reactant: CS(N)(=O)=O
Agent: Cl
Solvent: O=S(Cl)Cl
Product: CS(=O)(=O)NC(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 110 °C

Procedure:
5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (2 gm) is heated under reflux in excess of thionyl chloride (20 ml) for 90 minutes. The excess thionyl chloride is removed under vacuum. The residual product is mixed with at least 1.5 mole equivalent CH3SO2NH2, heated slowly in an oil bath to about 110° C. The reaction temperature is slowly raised to about 150° C. and kept at that temperature for at least 30 minutes or till the HCl ceases to evolve. The reaction mixture is cooled and the residue is crystallized from isopropanol to give 5-(2chloro-4-trifluoromethylphenoxy)-2-nitro-N-methansulphonyl benzamide, m.p. 201° C. In a similar way, but using the appropriate sulphonamide in place of methanesulphonamide, the corresponding nitrobenzoic acid sulphonamides are obtained, giving the following melting points 162° C., 179° C., 185° C., 170° C., 101° C., from the reaction with ethyl, propyl, butyl, hexyl and trifluoromethanesulphonamide respectively.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12][C:13]3[CH:14]=[C:15]([C:19]4([C:25]#[N:26])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH:8]=2)[N:3]=1.CCO.O.[NH2:31][NH2:32]>>[NH:31]([C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12][C:13]3[CH:14]=[C:15]([C:19]4([C:25]#[N:26])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH:8]=2)[N:3]=1)[NH2:32]
Reactant: NN
Reactant: N#CC1(c2cccc(Sc3ccc4nc(Cl)ccc4c3)c2)CCOCC1
Solvent: CCO
Solvent: O
Product: N#CC1(c2cccc(Sc3ccc4nc(NN)ccc4c3)c2)CCOCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
5h (4.4 g, 11.6 mmol) was suspended in hydrazine hydrate (11 mL) and EtOH (45 mL) and heated to 80° C. overnight. The reaction was cooled to room temperature and concentrated, and then diluted with EtOAc and water. The aqueous layer was extracted with EtOAc twice, and the combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was dissolved in CH2Cl2 (15 mL) and heated to dissolve as much of the material as possible. Hexanes (45 mL) was added slowly, and the mixture was stirred for 30 minutes. The precipitate was filtered, rinsed with hexanes, and dried to give the desired product, 5i.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[NH:12])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:3].C(N(CC)CC)C.[C:20](Cl)(=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22]>ClCCl>[CH3:22][C:21]([CH3:24])([CH3:23])[C:20]([N:12]=[C:5]([O:4][CH2:2][CH3:3])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:25]
Reactant: CCOC(=N)CC(=O)OCC
Reactant: CC(C)(C)C(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CC(=NC(=O)C(C)(C)C)OCC
Temperature: -15 °C
Reaction time: 18 h
Yield: 70.6 %

Procedure:
Ethyl 3-Ethoxy-3-iminopropanoate Hydrochloride (Preparation 118, 50 g, 0.256 mol) was suspended in dichloromethane (600 mL). The suspension was cooled to −15° C. and triethylamine (7.8 mL, 0.56 mol) followed by pivaloyl chloride (31.5 mL, 0.256 mol) were added. The reaction mixture was left for 18 hours at room temperature, then washed with water, dried over MgSO4, and evaporated. The residue was triturated with hexane. The resulting precipitate was filtered and dried to afford the title compound (44 g, 70%). Taken directly on to the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23]([OH:25])=O)=[CH:13][C:12]=2[N:11]=1.S(Cl)(Cl)=O.[F:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1.[H-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23]([NH:35][C:34]3[CH:36]=[CH:37][C:31]([F:30])=[CH:32][CH:33]=3)=[O:25])=[CH:13][C:12]=2[N:11]=1
Reactant: Cc1nc2c(o1)c(C(=O)O)cc1nc(Nc3c(F)cccc3Cl)[nH]c12
Reactant: Nc1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O=S(Cl)Cl
Product: Cc1nc2c(o1)c(C(=O)Nc1ccc(F)cc1)cc1nc(Nc3c(F)cccc3Cl)[nH]c12
Yield: 31.9 %

Procedure:
The title compound was prepared following the procedure as described for Example-177 using 7-[(2-chloro-6-fluorophenyl)amino]-2-methyl-8H-imidazo[4,5-e][1,3]benzoxazole-4-carboxylic acid (Intermediate-56, 0.050 g, 0.138 mmol), thionyl chloride (2.0 mL), 4-fluoro aniline (0.052 g, 0.138 mmol), THF (5.0 mL) and 60% NaH (0.017 g, 0.692 mmol). The obtained product was further purified by column chromatography on neutral alumina eluting with 1.5-2.0% MeOH: DCM to afford 0.020 g of the desired product. 1HNMR (DMSO-d6): δ 2.65 (s, 3H), 7.20 (t, J=7.8 Hz, 2H), 7.40-7.46 (m, 3H), 7.63 (s, 1H), 7.80-7.82 (m, 2H), 9.34 (s, 1H), 10.08 (s, 1H), 11.63 (s, 1H); MS [M−H]−: 452.23.
Reaction SMILES: [CH3:1][C:2]1([CH3:48])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@H:12]3[O:16][C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][C:29]4[CH:30]=[C:31]([NH:35][C:36]([NH:38][C:39]5[CH:44]=[CH:43][CH:42]=[C:41]([N+:45]([O-])=O)[CH:40]=5)=[O:37])[CH:32]=[CH:33][CH:34]=4)[CH2:13]3)=[CH:11][C:5]=2[CH2:4][O:3]1>CCO.CCOC(C)=O.[Pt]=O>[NH2:45][C:41]1[CH:40]=[C:39]([NH:38][C:36]([NH:35][C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([CH2:28][O:27][CH2:26][CH2:25][O:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][N:14]3[CH2:13][C@@H:12]([C:10]4[CH:9]=[CH:8][C:6]5[O:7][C:2]([CH3:1])([CH3:48])[O:3][CH2:4][C:5]=5[CH:11]=4)[O:16][C:15]3=[O:17])[CH:30]=2)=[O:37])[CH:44]=[CH:43][CH:42]=1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(NC(=O)Nc5cccc([N+](=O)[O-])c5)c4)C(=O)O3)ccc2O1
Agent: O=[Pt]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(NC(=O)Nc5cccc(N)c5)c4)C(=O)O3)ccc2O1
Yield: 99.8 %

Procedure:
A solution of N-[3-({2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy}methyl)phenyl]-N′-(3-nitrophenyl)urea (0.976 g) in EtOH (12 ml) and EtOAc (12 ml) was hydrogenated over platinum oxide (0.020 g) for 2 h. The mixture was filtered through celite and washed with EtOH. Solvent evaporation in vacuo gave the title compound (0.93 g). LCMS RT=3.48 min, ES+ve 633 (MH)+.
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10].S(Cl)([Cl:14])=O>N1C=CC=CC=1.ClCCl>[Cl:14][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10]
Reactant: C=CCCCCCCCCO
Reactant: O=S(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: C=CCCCCCCCCCl
Yield: 95.3 %

Procedure:
To 26.0 g of 9-decene-1-ol was added 10-drops of pyridine and the mixture was placed into an eggplant flask. To the eggplant flask was added dropwise 24.0 g of thionyl chloride during cooling with ice. After dropping, the mixture was reacted for 8.5 hours at 70° C. After the conclusion of the reaction, the reaction product was diluted with dichloromethane and then washed with an aqueous potassium carbonate solution. The reaction solution was then dried over magnesium sulfate and subsequently concentrated under reduced pressure. The resulting residue was purified by column chromatography to obtain 27.7 g of 10-chloro-1-decene. (Yield: 95%)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10](O)[C:11]3[CH2:16][CH2:15][CH2:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:20])=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([Cl:20])[C:11]3[CH2:16][CH2:15][CH2:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1
Reactant: Oc1nc(-c2ccc(Cl)cc2)nc2c1CCC2
Reactant: O=P(Cl)(Cl)Cl
Product: Clc1ccc(-c2nc(Cl)c3c(n2)CCC3)cc1
Reaction time: 3 h

Procedure:
8.0 g of 2-(4-chlorophenyl)-4-hydroxy-6,7-dihydro-5H-cyclopenta[d]pyrimidine are heated to 100° C. in 10 ml of phosphorus oxychloride. After 3 hours, the cooled solution was cautiously poured onto ice water. The crystalline product was filtered off with suction, washed well with water and dried in vacuo at room temperature. Yield: 6.5 g. M.p.: 1450° C.