Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][CH2:2][CH:3]([CH:5]1[O:9][CH2:8][CH2:7][O:6]1)[CH3:4].[C:10]1([P:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C=CC=CC=1>[Br-:1].[O:6]1[CH2:7][CH2:8][O:9][CH:5]1[CH:3]([CH3:4])[CH2:2][P+:16]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CC(CBr)C1OCCO1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CC(C[P+](c1ccccc1)(c1ccccc1)c1ccccc1)C1OCCO1
Product: [Br-]
Yield: 74.6 %

Procedure:
A mixture of 110 g (0.56 mol) of 2-(1-bromopropan-2-yl)-1,3-dioxolane, 148.5 g (0.56 mol) of triphenylphosphine and 550 ml of anhydrous toluene is heated at reflux under nitrogen for 24 h. The paste-like salt phase is separated and washed with 5×200 ml of anhydrous ethyl ether. After drying under vacuum there are obtained 191 g of [2-(1,3-dioxolan-2-yl)propan-1-yl]triphenylphosphonium bromide (white solid; yield 75%).
Reaction SMILES: [CH:1]([NH:3][C:4]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:5]=1[C:6]([NH2:8])=[O:7])=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:23]=1[CH2:24]Br>CN(C)C=O>[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:23]=1[CH2:24][O:13][C:10]1[CH:11]=[CH:12][C:4]([NH:3][CH:1]=[O:2])=[C:5]([CH:9]=1)[C:6]([NH2:8])=[O:7]
Reactant: NC(=O)c1cc(O)ccc1NC=O
Reactant: COc1ccc(OC)c(CBr)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(OC)c(COc2ccc(NC=O)c(C(N)=O)c2)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 140 mg of 2-formylamino-5-hydroxybenzamide in 15 ml of dry dimethylformamide is treated subsequently with 160 mg of potassium carbonate and 180 mg of 2,5-dimethoxybenzylbromide. The mixture is stirred at room temperature for 4 hours, and then the solvent is distilled off in vacuo. The residue is partitioned between water and ethyl acetate, and the separated organic layer is dried over magnesium sulfate and evaporated in vacuo. Purification of the crude product thus obtained by silica gel chromatography (ethyl acetate) gives the title compound as colourless crystals. mp: 135-138°.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[N:11]1[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[NH:13][C:12]1=[O:22].[C:23](=O)([O-])[O-].[K+].[K+].CI>C(#N)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[N:11]1[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[N:13]([CH3:23])[C:12]1=[O:22]
Reactant: O=C([O-])[O-]
Reactant: O=c1cc(C(F)(F)F)[nH]c(=O)n1-n1ccc2c(Cl)cccc21
Agent: [K+]
Solvent: CI
Solvent: CC#N
Product: Cn1c(C(F)(F)F)cc(=O)n(-n2ccc3c(Cl)cccc32)c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 24.8 %

Procedure:
A mixture of 169B (0.88 g, 2.7 mmol), dry acetonitril (10 mL), potassium carbonate (0.41 g, 2.9 mmol) and methyl iodide (0.88 g, 6.2 mmol) is stirred overnight at room temperature. The solids are removed by filtration. The motherliquor is concentrated under reduced pressure. The residue obtained is purified by flash chromatography (ethyl acetate/petrol ether 2/8) to yield the product as a brown oil (0.23 g).
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:38])[C@@H:26]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:27]([O:32][CH3:33])[CH2:28][C:29]([OH:31])=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.FC(F)(F)C(O[C:50]1[C:55]([F:56])=[C:54]([F:57])[C:53]([F:58])=[C:52]([F:59])[C:51]=1[F:60])=O>ClCCl>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:38])[C@@H:26]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:27]([O:32][CH3:33])[CH2:28][C:29]([O:31][C:50]3[C:51]([F:60])=[C:52]([F:59])[C:53]([F:58])=[C:54]([F:57])[C:55]=3[F:56])=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Reactant: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)Oc1c(F)c(F)c(F)c(F)c1F)OC)N(C)C(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.2 %

Procedure:
To a solution of #@5 (19.43 g, 37.03 mmol, 1 eq.) in dichloromethane (100 mL) and pyridine (5.86 g, 74.1 mmol, 2 eq.) was added pentafluorophenyl trifluoroacetate (20.7 g, 74.1 mmol, 2 eq.) and the reaction was stirred at room temperature for 1 hour. The reaction was concentrated in vacuo and purified by silica gel chromatography (Gradient: 0 to 52% ethyl acetate in heptane) to afford #174 (23.58 g, 92%) as a yellow oil. LC-MS (Protocol Q1): m/z 691.2 [M+H+], retention time=1.23 minutes.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1([CH3:28])[CH2:14][NH:13][CH2:12][CH2:11][N:10]1[C:15]([C:17]1[N:21]=[CH:20][N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:18]=1)=[O:16].[CH3:29][NH:30][C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][C:39]=1[N+:40]([O-:42])=[O:41])[C:34](O)=[O:35].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:8][C:9]1([CH3:28])[CH2:14][N:13]([C:34](=[O:35])[C:33]2[CH:37]=[CH:38][C:39]([N+:40]([O-:42])=[O:41])=[C:31]([NH:30][CH3:29])[CH:32]=2)[CH2:12][CH2:11][N:10]1[C:15]([C:17]1[N:21]=[CH:20][N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:18]=1)=[O:16]
Reactant: CC1(C)CNCCN1C(=O)c1ncn(-c2ccccc2)n1
Reactant: CNc1cc(C(=O)O)ccc1[N+](=O)[O-]
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CNc1cc(C(=O)N2CCN(C(=O)c3ncn(-c4ccccc4)n3)C(C)(C)C2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 399 mg (1.00 mmol) (2,2-dimethyl-piperazin-1-yl)-(1-phenyl-1-H-[1,2,4]triazol-3-yl)-methanone trifluoroacetate, 196 mg (1.00 mmol) 3-methylamino-4-nitro-benzoic acid, 353 mg (1.10 mmol) TBTU and 600 μL (3.50 mmol) DIPEA in 1.00 mL DMF was stirred at RT for 1 h. The reaction mixture was poured into ice water. The precipitate was filtered off, washed with water and dried.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2]O.[NH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.O>>[OH:8][CH2:7][CH2:6][N:5]1[CH2:2][CH2:1][O:4][CH2:9][CH2:10]1.[O:8]1[CH2:9][CH2:10][N:5]([CH:6]([N:5]2[CH2:2][CH2:1][O:4][CH2:9][CH2:10]2)[CH3:7])[CH2:6][CH2:7]1
Reactant: C1COCCN1
Reactant: OCCO
Solvent: O
Product: CC(N1CCOCC1)N1CCOCC1
Product: OCCN1CCOCC1
Temperature: 150 °C
Yield: 17 %

Procedure:
A 22 ml stainless steel Parr bomb reactor was charged with 5.5 g ethylene glycol (88.6 mmol), 1.0 g morpholine (11.5 mmol), 42 mg RuCl3 ×H2O(1.7×10-4 mol) 0.52 g N-methylpyrrolidone (as internal standard) and a magnetic stirring bar in a nitrogen-filled glove box. The bomb was sealed and placed in a previously-heated oil bath with stirring. After heating for 2.5 h at 150° C. the reactor pressure was 20 psig. At this point, the bomb was cooled to room temperature at which point the pressure stood at 6 psig. The reactor was vented, opened, and the contents analyzed by GLC. The conversion of morpholine was 100% with yields of hydroxyethylmorpholine and bismorpholinoethane being 17% and 79%, respectively (r=0.82).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])/[CH:5]=[C:6](/[C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[C:15]([Br:20])[CH:14]=1)\[C:7]1[S:8][C:9]([CH3:12])=[CH:10][N:11]=1)[CH3:2]>C(OCC)C.CC(O)=O.CCOC(C)=O.[Zn]>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][CH:6]([C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[C:15]([Br:20])[CH:14]=1)[C:7]1[S:8][C:9]([CH3:12])=[CH:10][N:11]=1)[CH3:2]
Reactant: CCOC(=O)/C=C(/c1cc(Cl)cc(Br)c1)c1ncc(C)s1
Agent: [Zn]
Solvent: CCOCC
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CCOC(=O)CC(c1cc(Cl)cc(Br)c1)c1ncc(C)s1
Reaction time: 8 h
Yield: 94 %

Procedure:
18 g (46.55 mmol) of (Z)-3-(3-Bromo-5-chloro-phenyl)-3-(5-methyl-thiazol-2-yl)-acrylic acid ethyl ester are dissolved in 250 ml Diethylether and 80 ml AcOH. 3 Eq (140 mmol) of zinc dust are added over a period of 60 minutes. The resulting mixture is allowed to stir overnight, diluted with 100 ml EtOAc and filtrated over a pad of Celite. The solvent is removed in vacuo, the residue taken up in EtOAc, washed with brine and dried over MgSO4. After evaporation of the solvent 17 g (Yield=99%) of crude product are obtained, which are used in the last step.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH:10]C(OC(C)(C)C)=O)=[CH:5][CH:4]=1.[Cl:20][C:21]1[CH:31]=[CH:30][C:29]([S:32](=[O:38])(=[O:37])[NH:33][CH:34]2[CH2:36][CH2:35]2)=[CH:28][C:22]=1[C:23]([N:25]=[C:26]=[O:27])=O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:20][C:21]1[CH:31]=[CH:30][C:29]([S:32]([NH:33][CH:34]2[CH2:36][CH2:35]2)(=[O:38])=[O:37])=[CH:28][C:22]=1[C:23]1[NH:25][C:26](=[O:27])[N:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:4][CH:5]=2)[N:10]=1
Reactant: O=C=NC(=O)c1cc(S(=O)(=O)NC2CC2)ccc1Cl
Reactant: CC(C)(C)OC(=O)NNc1ccc(C(F)(F)F)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=c1[nH]c(-c2cc(S(=O)(=O)NC3CC3)ccc2Cl)nn1-c1ccc(C(F)(F)F)cc1
Yield: 60.5 %

Procedure:
The title compound was prepared by following the procedure as described for Example-83 by using tert-butyl 2-(4-(trifluoromethyl)phenyl)hydrazinecarboxylate (Intermediate-53, 0.050 g, 0.18 mmol), 2-chloro-5-(N-cyclopropylsulfamoyl)benzoyl isocyanate (step-4 of Intermediate-40, 0.108 g, 0.36 mmol), DCM (10 mL) and TFA (3 mL) to afford 0.050 g of desired product. 1H NMR (400 MHz, DMSO d6): δ 0.40-0.42 (m, 2H), 0.50-0.54 (m, 2H), 2.17-2.21 (m, 1H), 7.85 (d, J=8.8 Hz, 2H), 7.92-7.98 (m, 2H), 8.15-8.21 (m, 4H), 12.84 (s, 1H); MS (m/z): 457.15 (M+H+).
Reaction SMILES: Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=1.[NH2:32][C:33]1[CH:41]=[C:40]2[C:36]([CH2:37][CH2:38][N:39]2[C:42](=[O:47])[C:43]([CH3:46])([OH:45])[CH3:44])=[CH:35][C:34]=1[O:48][CH3:49].[CH3:50][NH2:51].[OH-].[K+]>C1COCC1.C(OCC)(=O)C>[F:18][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:8][C:7]2[N:16]=[C:3]([NH:32][C:33]3[CH:41]=[C:40]4[C:36]([CH2:37][CH2:38][N:39]4[C:42](=[O:47])[C:43]([OH:45])([CH3:44])[CH3:46])=[CH:35][C:34]=3[O:48][CH3:49])[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]=23)[C:14]=1[C:15]([NH:51][CH3:50])=[O:17]
Reactant: COc1cc2c(cc1N)N(C(=O)C(C)(C)O)CC2
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c2nc(Cl)n2c(=O)c4c(F)cccc4nc32)cc1
Reactant: CN
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CNC(=O)c1c(F)cccc1Nc1nc(Nc2cc3c(cc2OC)CCN3C(=O)C(C)(C)O)[nH]c2nccc1-2
Temperature: 65 °C
Reaction time: 8 h
Yield: 38.7 %

Procedure:
A suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (300 mg, 0.63 mmol) and 1-[6-amino-5-(methyloxy)-2,3-dihydro-1H-indol-1-yl]-2-methyl-1-oxo-2-propanol (157 mg, 0.63 mmol) in THF(250 ml) was heated at 65° C. for 4 hrs. The reaction was diluted with ethyl acetate (200 ml) and washed with saturated NaHCO3 (300 ml). Organic layer was removed, concentrated by rotary evaporation, solids triturated from ethyl acetate/hexanes, and dried under house vacuum prior to next step. ESIMS (M+H)+=657. The solids were then added to THF (200 ml) followed by a solution of methylamine (2M in THF, 11.42 ml, 22.84 mmol) and the resulting mixture was stirred at rt overnight. Next, the crude reaction was adsorbed onto silica gel and purified by silica gel chromatography (DCM to 10% MeOH/DCM over 30 min). ESIMS (M+H)+=688. The isolated pure amide was redissolved in 1,4-dioxane (10 ml), and potassium hydroxide (8.72 ml, 8.72 mmol) was added and the reaction was heated in the microwave at 120° C. for 20 min. The resulting solution was adsorbed onto silica gel and purified by silica gel chromatography (DCM to 10% MeOH/DCM) to afford the title compound (0.130 g, 39% over three steps). ESIMS (M+H)+=534. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (s, 6 H) 2.80 (d, J=4.41 Hz, 3 H) 3.06 (t, J=8.03 Hz, 2 H) 3.78 (s, 3 H) 4.43 (t, J=8.23 Hz, 2 H) 5.42 (s, 1 H) 6.26-6.27 (m, 1 H) 6.85-6.93 (m, 1 H) 6.93 (m, 1 H) 6.96 (s, 1 H) 7.28-7.38 (m, 1 H) 7.55 (s, 1 H) 8.37 (d, J=8.43 Hz, 1 H) 8.51-8.58 (m, 1 H) 8.62 (s, 1 H) 10.17 (s, 1 H) 11.26 (s, 1 H).
Reaction SMILES: [C:1]([O:5][C:6]([CH2:8][CH:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:24]([C:31]1[S:35][C:34]([NH2:36])=[N:33][N:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH2:24]([C:31]1[S:35][C:34]([NH:36][C:19]([C:18]2[CH:17]=[CH:16][C:15]([CH:12]3[CH2:13][CH2:14][CH:9]([CH2:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][CH2:11]3)=[CH:23][CH:22]=2)=[O:21])=[N:33][N:32]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)(C)OC(=O)CC1CCC(c2ccc(C(=O)O)cc2)CC1
Reactant: Nc1nnc(Cc2ccccc2)s1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)CC1CCC(c2ccc(C(=O)Nc3nnc(Cc4ccccc4)s3)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 34 %

Procedure:
0.45 g of 4-(4-tert-butoxycarbonylmethylcyclohexyl)benzoic acid (1.41 mmol, 1 eq.) is placed in a mixture of 5 mL of dimethylformamide at room temperature. 0.539 g of 5-benzyl-1,3,4-thiadiazol-2-amine (2.82 mmol, 2 eq.), 0.791 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (1.70 mmol, 1.2 eq.) and 0.49 mL of diisopropylethylamine (2.83 mmol, 2 eq.) are successively added. The reaction mixture is stirred for 16 hours at room temperature, diluted in ethyl acetate and washed three times with water. The organic phase is concentrated. The residue is taken up and washed with ethanol, filtered and dried. 0.236 g of tert-butyl {4-[4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenyl]cyclohexyl}acetate is obtained.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[S:16][CH3:17])[C:10](O)=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.S(Cl)([Cl:20])=O>C1(C)C=CC=CC=1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[S:16][CH3:17])[C:10]([Cl:20])=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CSc1ccc(C(=O)O)cc1OC1CCCC1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CSc1ccc(C(=O)Cl)cc1OC1CCCC1

Procedure:
3-Cyclopentyloxy-4-(methylthio)benzoic acid (0.7 g; that is prepared as described in Reference Example 55) is dissolved in toluene (20 mL) and heated at 80° C. for 1 hour 30 minutes in the presence of thionyl chloride (5 mL). Concentration gave 3-cyclopentyloxy-4-(methylthio)benzoyl chloride (0.76 g), in the form of a yellow oil.
Reaction SMILES: [ClH:1].[NH2:2][CH:3]1[C:11]2[C:6](=[C:7](C)[CH:8]=[C:9]([CH2:13][NH:14]C(=O)C[Cl:17])[C:10]=2[OH:12])[CH2:5][CH2:4]1.Cl.[CH2:21](O)C>>[ClH:17].[ClH:1].[NH2:2][C:3]1([CH3:21])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:13][NH2:14])[C:10]=2[OH:12])[CH2:5][CH2:4]1
Reactant: CCO
Reactant: Cc1cc(CNC(=O)CCl)c(O)c2c1CCC2N
Agent: Cl
Product: CC1(N)CCc2ccc(CN)c(O)c21

Procedure:
5 Grams of 1-amino-4-methyl-6-α-chloroacetylaminomethyl-7-hydroxyindane hydrochloride and 100 ml of ethanol containing 50 ml of concentrated hydrochloric acid were refluxed by heating for 8 hours. The solvent was removed by evaporation and the residue obtained was washed with ethanol. Recrystallized from methanol-ether to obtain 1 g of 1-amino-methyl-6-aminomethyl-7-hydroxyindane dihydrochloride.
Reaction SMILES: [O:1]1[CH:5]=[C:4]([CH2:6][CH2:7][NH2:8])[C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2.[CH:13](OCC)=[O:14].Cl>>[CH:13]([NH:8][CH2:7][CH2:6][C:4]1[C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]=2[O:1][CH:5]=1)=[O:14]
Reactant: CCOC=O
Reactant: NCCc1coc2ccccc12
Agent: Cl
Product: O=CNCCc1coc2ccccc12

Procedure:
A solution of 2.35 g (0.015 mole) of 2-(3benzo[b]furanyl)ethylamine and 5 mL of ethyl formate was heated at 60° C. for 3 hours, poured into 2N HCl and washed with methylene chloride which in turn was washed with 5% sodium hydroxide (w/v), dried (MgSO4) , filtered and concentrated to give 2.70 g of product.
Reaction SMILES: [CH2:1]([NH:4][C:5]([C:7]1[S:11][C:10]([Br:12])=[N:9][C:8]=1[Br:13])=O)[CH:2]=[CH2:3].P(Cl)(Cl)(Cl)(Cl)Cl.Cl.O1CCOCC1.CO[CH:29](OC)[CH2:30][NH2:31]>ClCCl.O>[CH2:1]([N:4]1[CH:29]=[CH:30][N:31]=[C:5]1[C:7]1[S:11][C:10]([Br:12])=[N:9][C:8]=1[Br:13])[CH:2]=[CH2:3]
Reactant: C=CCNC(=O)c1sc(Br)nc1Br
Reactant: COC(CN)OC
Agent: Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: O
Solvent: C1COCCO1
Solvent: ClCCl
Product: C=CCn1ccnc1-c1sc(Br)nc1Br
Temperature: 60 °C
Reaction time: 16 h
Yield: 57.7 %

Procedure:
To a solution of N-allyl-2,4-dibromo-1,3-thiazole-5-carboxamide (13.0 g, 39.9 mmol) in dichloromethane (260 mL) was added phosphorus pentachloride (9.93 g, 47.7 mmol) and 4M hydrochloric acid in dioxane (1.52 mL, 6.06 mmol). The reaction was heated to 60° C. for 90 minutes under an atmosphere on nitrogen. The reaction was allowed to cool to room temperature and then aminoacetaldehyde dimethyl acetal (47.8 mL, 439 mmol) was added slowly through the condenser. The mixture was heated to 60° C. for 2 hours under an atmosphere of nitrogen then cooled to room temperature, and water was added (200 mL). The layers were separated and the organic phase was washed with water again (2×200 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and washed with dichloromethane (200 mL). To this dichloromethane solution of the intermediate was added 4M hydrochloric acid in dioxane (120 mL, 480 mmol) and the solution was stirred at 60° C. for 16 hours. The solution was decanted (leaving behind an oily black residue on the flask) then the solvent was evaporated and the residue was diluted with ethyl acetate and saturated sodium bicarbonate solution. The layers were separated and the aqueous phase was extracted three more times with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography was performed to yield the title compound (8.04 g, 58%). LCMS: (FA) ES+ , 306 (parent minus allyl group). 1H NMR (300 MHz, d4-methanol) δ: 7.37-7.31 (m, 1H), 7.20-7.16 (m, 1H), 6.02-5.86 (m, 1H), 5.26-5.18 (m, 1H), 5.07-4.96 (m, 1H), 4.68-4.59 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH:4]([O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)[CH2:5][CH2:6][OH:7].C(N(CC)CC)C.[CH3:24][C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1>ClCCl>[CH3:1][O:2][C:3](=[O:16])[CH:4]([O:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=1)[CH2:5][CH2:6][O:7][S:31]([C:28]1[CH:29]=[CH:30][C:25]([CH3:24])=[CH:26][CH:27]=1)(=[O:33])=[O:32]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)C(CCO)Oc1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C(CCOS(=O)(=O)c1ccc(C)cc1)Oc1ccc(Cl)cc1
Temperature: 22 °C
Reaction time: 48 h
Yield: 46 %

Procedure:
To a solution of 2-(4-Chloro-phenoxy)-4-hydroxy-butyric acid methyl ester (Example 473b), 0.225 g) in dichloromethane (1.88 mL) at room temperature, was added triethylamine (116 mg) and 4-methylbenzene-1-sulfonyl chloride (177 mg). The mixture was stirred at 22° C. for 48 hr. The reaction mixture was partitioned between water and ethyl acetate. The phases were separated. The aqueous layer was extracted with ethyl acetate. The organic layers were washed with brine, dried over Na2SO4 and filtered. The crude mixture was concentrated to dryness and purified by chromatography on silica gel to yield the title compound as a colorless oil (169 mg; 46%). MS (ESI): m/z=419 [M+NH4]+.
Reaction SMILES: [OH:1][C:2]1[C:3](=[O:10])[CH:4]=[C:5]([OH:9])[C:6](=[O:8])[CH:7]=1.Cl.CC(C)=O.CC1(C)OC2C=C3OC(C)(C)OC3=CC=2O1>O.[Fe]>[OH:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([OH:9])=[CH:4][C:3]=1[OH:10]
Reactant: O=C1C=C(O)C(=O)C=C1O
Agent: [Fe]
Agent: CC1(C)Oc2cc3c(cc2O1)OC(C)(C)O3
Agent: Cl
Solvent: CC(C)=O
Solvent: O
Product: Oc1cc(O)c(O)cc1O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2,5-Dihydroxy-1,4-benzoquinone (10.00 g, 71.43 mmol) was suspended in water (200 ml, distilled) followed by HCl (6 mL, 142-86 mmol, conc.). Iron (4.00 g, 71.43 mmol, powder) was added and the mixture was stirred 30 minutes at room temperature. The solution was filtered and the solution evaporated to dryness. The product was isolated as a grey brown powder containing some iron complexes. Yield 14.80 g. The product is used as such in the reaction with acetone and P2O5 (Example 5) with no negative effects.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C1=CC2C3C=CC(C3)C2C1
Reactant: C[SiH](Cl)Cl
Agent: Cl[Pd]Cl
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCCCCCCCCCCCCCCC
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 2 h
Yield: 337.4 %

Procedure:
As described in Example 2, 2.85 g (0.0216 mol) of dicyclopentadiene, 3.72 g (0.0323 mol) of methyldichlorosilane, 0.040 g (0.000226 mol) of palladium dichloride, 0.19 g (0.000451 mol) of 1,4-bis(diphenylphosphino)butane and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 2 hours. Products were subject to simple vacuum distillation, thereby providing a mixture (13.2 g) of (2-cyclopentenyl)methyldichlorosilane (4.1 g, 70%), other unreacted reactants, toluene, hexadecane, and unidentified compounds.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[C:5]([NH2:16])[CH:4]=1.[S:17]1[CH:21]=[CH:20][C:19](/[CH:22]=[CH:23]/[C:24](Cl)=O)=[CH:18]1.N1C=CC=CC=1N1C2C=CC=CC=2N=C1/C=C/C1C=CC=CC=1.[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52]>C(OCC)(=O)C>[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52].[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]2[N:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=3)[C:24](/[CH:23]=[CH:22]/[C:19]3[CH:20]=[CH:21][S:17][CH:18]=3)=[N:16][C:5]=2[CH:4]=1
Reactant: O=C(Cl)/C=C/c1ccsc1
Reactant: COc1ccc(Nc2ccccn2)c(N)c1
Agent: C(=C/c1nc2ccccc2n1-c1ccccn1)\c1ccccc1
Agent: O=C(O)C(=O)O
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)nc(/C=C/c1ccsc1)n2-c1ccccn1

Procedure:
Free base of the titled compound was prepared from 4-methoxy-2-amino-N-(2-pyridyl)aniline and (E)-3-(3-thienyl)acryloyl chloride according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A). The free base and oxalic acid were dissolved into ethyl acetate. Concentration and recrystallization from ethyl acetate/n-hexane yielded the titled compound.