Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[CH3:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[C:17](O)=[O:18]>>[CH3:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[C:17]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:12])=[N:9]2)=[CH:4][CH:3]=1)=[O:18]
Reactant: Cc1cc(C(=O)O)ccc1-c1ccncc1
Reactant: Cc1ccc2ccc(N)cc2n1
Product: Cc1ccc2ccc(NC(=O)c3ccc(-c4ccncc4)c(C)c3)cc2n1

Procedure:
Using the procedure outlined in Example 56, the title compound was prepared from 7-amino-2-methylquinoline (D66) (30 mg, 0.19 mmol) and 3-methyl-4-(4-pyridyl)benzoic acid (D57) (49 mg, 0.23 mmol) as an orange gum, (59 mg, 88%). 1H NMR (250 MHz, CDCl3) δ (ppm): 8.70 (dd, 2H), 8.10 (s, 2H), 8.03 (m, 2H), 7.87 (s, 1H), 7.80 (d, 2H), 7.35 (d, 1H), 7.27 (m, 3H), 2.74 (s, 3H), 2.37 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[Cl:16])[O:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.N1C=CC=CC=1.[CH3:23][N:24]1[C:28]([C:29](Cl)=[O:30])=[CH:27][C:26]([CH3:32])=[N:25]1>O1CCCC1>[NH2:12][C:9]1[N:10]=[CH:11][C:6]([O:5][C:4]2[CH:13]=[CH:14][C:15]([Cl:16])=[C:2]([NH:1][C:29]([C:28]3[N:24]([CH3:23])[N:25]=[C:26]([CH3:32])[CH:27]=3)=[O:30])[CH:3]=2)=[CH:7][CH:8]=1
Reactant: Cc1cc(C(=O)Cl)n(C)n1
Reactant: Nc1ccc(Oc2ccc(Cl)c(N)c2)cn1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: Cc1cc(C(=O)Nc2cc(Oc3ccc(N)nc3)ccc2Cl)n(C)n1
Yield: 10 %

Procedure:
In the same manner as in Reference Example 3 and using 5-(3-amino-4-chlorophenoxy)pyridin-2-amine (2.01 g, 8.55 mmol), pyridine (725 μL, 8.98 mmol), 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (1.42 g, 8.98 mmol) and tetrahydrofuran (50 mL) as starting materials, the title compound (306 mg, 10%) was obtained as a white solid.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][O:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:27][C:28]1[CH:35]=[C:34]([CH3:36])[C:31]([CH:32]=[O:33])=[C:30]([CH3:37])[CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC>C(N(CC)CC)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@@H:15]([O:16][CH2:17][CH3:18])[C@@H:32]([C:31]1[C:30]([CH3:37])=[CH:29][C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:35][C:34]=1[CH3:36])[OH:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(OCc2ccccc2)cc(C)c1C=O
Reactant: CCOCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCN(CC)CC
Product: CCO[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)[C@H](O)c1c(C)cc(OCc2ccccc2)cc1C

Procedure:
In analogy to the procedure described in example 48 d], (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one (for the preparation of (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one see: D. Haigh, H. C. Birrell, B. C. C. Cantello, D. S. Eggleston, R. C. Haltiwanger, R. M. Hindley, A. Ramaswamy, N.C. Stevens, Tetrahedron: Asymmetry 1999, 10, 1353–1367) was reacted with 4-benzyloxy-2,6-dimethyl-benzaldehyde in the presence of triethylamine and di-n-butylboron triflate to give (S)-4-benzyl-3-[(2S,3R)-3-(4-benzyloxy-2,6-dimethyl-phenyl)-2-ethoxy-3-hydroxy-propionyl]-oxazolidin-2-one as colorless liquid. According to 1H-NMR spectroscopy, one of the four isomers is strongly predominating. The configuration was tentatively assigned as 2S,3R according to D. Haigh et al., Tetrahedron: Asymmetry 1999, 10, 1353–1367.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:21]3[C:20](=[O:30])[NH:19][C:18](=[O:31])[N:17]([CH3:32])[C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:21]3[C:20](=[O:30])[N:19]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[C:18](=[O:31])[N:17]([CH3:32])[C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cn1c(=O)[nH]c(=O)c2c1nc(N1CCN(C(=O)OC(C)(C)C)CC1)n2Cc1ccccc1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1c(=O)c2c(nc(N3CCN(C(=O)OC(C)(C)C)CC3)n2Cc2ccccc2)n(C)c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-[7-(Benzyl)-3-methyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperazine-1-carboxylic acid tert-butyl ester (182 mg) was dissolved in N,N-dimethylformamide (2 ml), and potassium carbonate (90 mg) and ethyl bromoacetate (0.06 ml) were added thereto. The reaction solution was stirred at room temperature overnight, diluted with ethyl acetate, and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[C:11]([N+:19]([O-])=O)[CH:12]=[CH:13][CH:14]=3)[C:9](=[O:22])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[OH:23]S(O)(=O)=O.O=S(=O)=O.B(O)(O)O.[S]>>[OH:23][C:14]1[C:15]2[C:16](=[O:18])[C:17]3[C:8](=[CH:7][CH:6]=[CH:5][C:4]=3[NH2:1])[C:9](=[O:22])[C:10]=2[C:11]([NH2:19])=[CH:12][CH:13]=1
Reactant: O=S(=O)(O)O
Reactant: O=C1c2cccc([N+](=O)[O-])c2C(=O)c2cccc([N+](=O)[O-])c21
Agent: O=S(=O)=O
Agent: OB(O)O
Agent: [S]
Product: Nc1cccc2c1C(=O)c1c(O)ccc(N)c1C2=O

Procedure:
100 parts of 1,5-dinitroanthraquinone are reduced as indicated in Example 3 with 35% strength oleum in the presence of boric acid by means of sulphur. The batch is then discharged onto 4,000 parts of ice and the product is filtered off with suction. After washing until neutral, 98 parts of 1-hydroxy-4-amino-8-nitroanthraquinone are obtained in the form of a 38% strength presscake, which can be reduced, for example to give 1-hydroxy-4,8-diaminoanthraquinone.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[C:23][CH3:24])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:28].CCN(CC)CC>C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[C:23][CH3:24])=[CH:16][CH:15]=1)[C:10]([O:12][CH2:26][C:27](=[O:28])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:11])=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: O=C(CBr)c1ccccc1
Reactant: CC#CCOc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC#CCOc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)OCC(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 74.5 %

Procedure:
(S)-2-tert-Butoxycarbonylamino-3-(4-but-2-ynyloxy-phenyl)-propionic acid (380 mg) was dissolved in ethyl acetate (5.0 mL). A commercially available reagent of 2-bromoacetophenone (164 mg) and Et3N (115.7 μL) were added and the mixture was stirred at room temperature for 2 days. To the reaction solution was added ethyl acetate and the mixture was washed with water and a saturated brine in this order. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The product was purified by recrystallization in 15% ethyl acetate/n-hexane to obtain 2-oxo-2-phenyl-ethyl (S)-2-tert-butoxycarbonylamino-3-(4-but-2-ynyloxy-phenyl)-propionate (277 mg, yield 89% over 2 steps) as colorless crystal (LCMS m/z 452 (M+1) Rt 232 min.).
Reaction SMILES: [F:1][C:2]([F:37])([F:36])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=2)[C:11]2([OH:24])[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)=[CH:6][CH:5]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[F:34][C:32]([F:33])([F:35])[O:31][C:28]1[CH:27]=[CH:26][C:25]([CH:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:37])([F:1])[F:36])=[CH:5][CH:6]=2)[C:11]2([OH:24])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:30][CH:29]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(C(c2ccc(OC(F)(F)F)cc2)c2ccc(OC(F)(F)F)cc2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: OC1(C(c2ccc(OC(F)(F)F)cc2)c2ccc(OC(F)(F)F)cc2)CCNCC1
Temperature: 25 °C

Procedure:
A mixture of 3.0 grams (0.0057 mole) of tert-butyl 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxypiperidine carboxylate and 25 mL of methylene chloride was chilled in a wet ice bath. A solution of 2.63 mL trifluoro acetic acid and 5 mL methylene chloride was added dropwise to the reaction mixture during a 5-minute period. The wet ice bath was removed and the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was then warmed to reflux, and allowed to cool to ambient temperature. The reaction mixture was concentrated under reduced pressure. The residue can then be dissolved in 100 mL methylene chloride and reacted with 200 mL of an aqueous solution saturated with sodium carbonate. The methylene chloride layer can then be separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield the subject compound.
Reaction SMILES: O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=[C:4]([C:16]#[N:17])[CH:3]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[NH2:50][CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53]>O1CCOCC1>[C:16]([C:4]1[CH:3]=[C:2]([NH:50][CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=1)#[N:17]
Reactant: N#Cc1cc(O)c2cc(C(F)(F)F)ccc2n1
Reactant: CC(C)(C)OC(=O)CN
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)CNc1cc(C#N)nc2ccc(C(F)(F)F)cc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into a 25 mL vial, was placed a solution of 4-hydroxy-6-(trifluoromethyl)quinoline-2-carbonitrile (238 mg, 1.00 mmol, 1.00 equiv) in dioxane (2 mL), PyBrOP (217 mg, 0.47 mmol, 1.10 equiv), triethylamine (354 mg, 3.50 mmol, 2.50 equiv) and tert-butyl 2-aminoacetate hydrochloride (217 mg, 1.30 mmol, 1.30 equiv). The reaction mixture was stirred overnight at room temperature. The reaction was then quenched by the addition of 25 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate. The combined organic layers dried over anhydrous sodium sulfate and concentrated under vacuum. The residue purified by chromatography over a silica gel column with EtOAc/petroleum ether (1:1-1:10). The title compound was obtained as a white solid.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[CH2:10][CH2:9][C@H:8]([OH:11])[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[H-].[Na+].Cl[C:15]1[CH:24]=[N:23][C:22]2[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([O:25][CH3:26])[CH:21]=2)[N:16]=1>C1COCC1>[CH3:26][O:25][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][C:19]=1[O:27][CH3:28])[N:16]=[C:15]([O:11][C@@H:8]1[CH2:9][CH2:10][C@H:5]([O:4][C:1](=[O:3])[CH3:2])[CH2:6][CH2:7]1)[CH:24]=[N:23]2
Reactant: CC(=O)O[C@H]1CC[C@@H](O)CC1
Reactant: COc1cc2ncc(Cl)nc2cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc2ncc(O[C@H]3CC[C@@H](OC(C)=O)CC3)nc2cc1OC

Procedure:
A mixture of cis 4-acetoxy-cyclohexanol (632 mg, 4 mmole) and NaH (60%, 220 mg, 5.5 mmole) in 15 mL of anhydrous THF is refluxed for 0.5 hour before addition of 2-chloro-6,7-dimethoxyquinoxaline (674 mg, 3 mmole). The resulting mixture is continued to be refluxed for two hours. The residue after filtration and concentration is chromatographed on silica gel (ether) to provide acetic acid cis-4-(6,7-dimethoxyquinoxalin-2-yloxy)-cyclohexyl ester (m.p. 150-152° C.). Anal. Calcd. for C18H22N2O5: C, 62.42; H, 6.40; N, 8.09; Found: C, 62.39; H, 6.55; N, 7.82 and cis-4-(6,7-dimethoxyquinoxalin-2-yloxy)cyclohexanol (m.p. 148-150° C.). Anal. Calcd. for C16H20N2O4: C, 63.14; H, 6.62; N, 9.20; Found: C, 62.80; H, 6.76; N, 8.67.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][SH:24])=[CH:19][CH:18]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][S:24][C:2]2[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=2[O:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:19][CH:18]=1
Reactant: CCOC(=O)COc1ccccc1Br
Reactant: COc1ccc(CS)cc1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)COc1ccccc1SCc1ccc(OC)cc1
Yield: 79 %

Procedure:
To a solution of ethyl 2-(2-bromophenoxy)acetate (3.0 g, 0.0116 mol) in dioxane (30 mL) was added (4-methoxyphenyl)methanethiol (2.14 g, 0.0139 mol), Pd2(dba)3 (20 mg), xantphos (20 mg) and DIEA (3 mL). The mixture was degassed 4 times (N2) and heated at reflux for 3 h, concentrated, and the crude product was purified by column chromatography. (3 g, yield 79%) MS (ESI+) e/z: 355.1 [M+1]+.
Reaction SMILES: [OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.[CH3:36][N:37]([CH3:50])[C:38]([C:40]1([C:43]2[CH:48]=[CH:47][CH:46]=[C:45](Br)[N:44]=2)[CH2:42][CH2:41]1)=[O:39]>>[CH3:36][N:37]([CH3:50])[C:38]([C:40]1([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C:16]3[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]4[CH2:6][CH2:5][C@:4]([CH2:3][C:2]([OH:1])([CH3:35])[CH3:34])([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[O:9][C:8]4=[O:10])[CH3:12])=[CH:14][CH:15]=3)[N:44]=2)[CH2:42][CH2:41]1)=[O:39]
Reactant: CN(C)C(=O)C1(c2cccc(Br)n2)CC1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Product: C[C@@H](c1ccc(-c2cccc(C3(C(=O)N(C)C)CC3)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Yield: 66 %

Procedure:
The title compound was prepared from (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-ethyl}-1,3-oxazinan-2-one and 1-(6-bromo-pyridin-2-yl)-cyclopropanecarboxylic acid dimethylamide following a procedure analogous to that described in Example 1. Yield: 66% of theory; LC (method 1): tR=2.00 min; Mass spectrum (ESI+): m/z=542 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH2:14]O)[CH:11]=[CH:12][CH:13]=2)=[N:6][CH:7]=1.[CH3:16][C:17]1[N:22]=[C:21]2[NH:23][C:24](=[O:26])[O:25][C:20]2=[CH:19][CH:18]=1>>[CH3:16][C:17]1[N:22]=[C:21]2[N:23]([CH2:14][C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=4)[CH:9]=3)[C:24](=[O:26])[O:25][C:20]2=[CH:19][CH:18]=1
Reactant: Cc1ccc(-c2cccc(CO)c2)nc1
Reactant: Cc1ccc2oc(=O)[nH]c2n1
Product: Cc1ccc(-c2cccc(Cn3c(=O)oc4ccc(C)nc43)c2)nc1

Procedure:
Reaction of [3-(5-methylpyridin-2-yl)phenyl]methanol with 5-methyl-3H-oxazolo[4,5-b]pyridin-2-one under Mitsunobu conditions gives the desired 5-methyl-3-[3-(5-methylpyridin-2-yl)benzyl]-3H-oxazolo[4,5-b]-pyridin-2-one, ESI 332 (M+H).
Reaction SMILES: [N:1]1([CH2:6][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[OH:8])[CH:5]=[CH:4][N:3]=[CH:2]1.N1(CCO[C:23]2[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=2)[C:29](=[O:33])[CH2:28][CH2:27][CH2:26]3)C=CN=C1>>[N:1]1([CH2:6][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:8][C:23]2[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=2)[C:29](=[O:33])[CH2:28][CH2:27][CH2:26]3)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C1CCCc2cc(OCCn3ccnc3)ccc21
Reactant: OC(Cn1ccnc1)c1ccccc1
Product: O=C1CCCc2cc(OC(Cn3ccnc3)c3ccccc3)ccc21
Yield: 93.7 %

Procedure:
Following the procedure of Example 78, Step 3, but using 2.63 g (14.0 mmol) of 2-(1H-1-imidazolyl)-1-phenyl-1-ethanol and 2.0 g (12.3 mmol) of 6-[2-(1H-1-imidazolyl)ethoxy]-1,2,3,4-tetrahydro-1-naphthalenone, there was obtained 3.83 g (93.6% yield) of the product as a glass. The structure was confirmed by NMR and mass spectroscopy. MS m/z 333 (M+H+).
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=2)[CH2:6][C:5]1=[O:16])(=[O:3])[CH3:2].[N:17]1([CH2:22][C:23]2[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=2)[CH:21]=[CH:20][N:19]=[CH:18]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=2)[C:6](=[C:27]([OH:28])[C:26]2[CH:25]=[CH:24][C:23]([CH2:22][N:17]3[CH:21]=[CH:20][N:19]=[CH:18]3)=[CH:31][CH:30]=2)[C:5]1=[O:16])(=[O:3])[CH3:2]
Reactant: CC(=O)N1C(=O)Cc2cc([N+](=O)[O-])ccc21
Reactant: O=C(O)c1ccc(Cn2ccnc2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)N1C(=O)C(=C(O)c2ccc(Cn3ccnc3)cc2)c2cc([N+](=O)[O-])ccc21

Procedure:
Prepared analogously to Example 10(a) from 1-acetyl-5-nitro-indolinone and 4-(imidazol-1-ylmethyl)benzoic acid in dry DMF in the presence of TBTU, HOBT and Hunig's base.
Reaction SMILES: [CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][C@@H:25]3[CH2:27][O:26]3)[N:12]=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[C:7]=2[CH2:6]1)(=[O:4])=[O:3].[CH3:28][N:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[C:30]1=[O:44]>CCO.ClC(Cl)C>[OH:26][C@H:25]([CH2:24][N:11]1[C:8]2[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][C:7]=2[C:13]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:23])[F:22])=[CH:18][CH:19]=2)=[N:12]1)[CH2:27][N:41]1[CH2:40][CH2:39][CH:38]([N:31]2[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[N:29]([CH3:28])[C:30]2=[O:44])[CH2:43][CH2:42]1
Reactant: Cn1c(=O)n(C2CCNCC2)c2ccccc21
Reactant: CS(=O)(=O)N1CCc2c(c(-c3ccc(C(F)(F)F)cc3)nn2C[C@@H]2CO2)C1
Solvent: CC(Cl)Cl
Solvent: CCO
Product: Cn1c(=O)n(C2CCN(C[C@H](O)Cn3nc(-c4ccc(C(F)(F)F)cc4)c4c3CCN(S(C)(=O)=O)C4)CC2)c2ccccc21
Yield: 63.4 %

Procedure:
A solution of (R)-5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (134 mg, 0.334 mmol) and 1-methyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one (110 mg, 0.476 mmol) in EtOH (0.8 mL) and dichloroethane (0.8 mL) was heated to 80° C. for 18 h. The mixture was then concentrated and the residue purified by column chromatography (silica, 0-50% acetone/CH2Cl2) to give the title compound (134 mg, 86%). TLC (20% acetone/CH2Cl2) Rf=0.3. MS (electrospray): calculated for C30H36F3N6O4S, [M +H]+ 633.24; m/z found, 633.3. 1H NMR (CDCl3, 400 MHz): 7.72 and 7.66 (A and B of M′BB′, Jab=8.3 Hz, 4H), 7.15 (dd, J=7.0, 1.7 Hz, 1H ), 7.08 (m, 2H), 6.98 (dd, J=6.6, 1.8 Hz, 1H), 4.60 and 4.55 (A and B of AB, Jab=14.5 Hz, 2H), 4.34 (m, 1H), 4.23 (dd, J=13.8, 2.8 Hz, 1H), 4.15 (m, 1H), 4.23 (dd, J=13.8, 6.6 Hz, 1H), 3.71 (m, 2H), 3.40 (s, 3H), 3.08 (m, 2H), 2.96 (m, 2H), 2.89 (s, 3H), 2.56-2.36 (m, 4H), 2.23 (d, J=11.6 Hz, 1H), 1.81 (m, 2H).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([SH:10])=[CH:6][CH:5]=1.I[C:12]1[N:13]=[C:14]([CH3:27])[NH:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=1>CN1C(=O)CCC1>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([S:10][C:12]2[N:13]=[C:14]([CH3:27])[NH:15][C:16]=2[C:17]2[CH:18]=[CH:19][C:20]([S:23]([CH3:26])(=[O:24])=[O:25])=[CH:21][CH:22]=2)=[CH:6][CH:5]=1
Reactant: Cc1nc(I)c(-c2ccc(S(C)(=O)=O)cc2)[nH]1
Reactant: Sc1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: Cc1nc(Sc2ccc(Cl)cc2)c(-c2ccc(S(C)(=O)=O)cc2)[nH]1
Reaction time: 0.25 h

Procedure:
To NaH (60% in mineral oil, 0.12 g, 3.0 mmol) in NMP (10 mL) was added 4-chlorobenzenethiol (0.44 g, 3.0 mmol). After stirring for 15 min, the reaction mixture was added to the product of Step 3 (1.09 g, 3.0 mmol) and CuBr (0.65 g, 4.5 mmol) in NMP (10 mL) under argon. The resulting mixture was kept at 140° C. for 4 h. After cooling, the reaction mixture was partitioned between H2O and EtOAc. The organic layer was separated, filtered through a thin pad of silica gel, and the filtrate was dried over anhydrous Na2SO4, and concentrated. The residue was purified by chromatography on silica gel (DCM to EtOAc) to give 4-[(4-chlorophenyl)thio]-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-imidazole. LCMS: [M+1]+=379.0
Reaction SMILES: [C:1]1(C)[C:2](S(O)(=O)=O)=[CH:3][C:4](S(O)(=O)=O)=[CH:5][CH:6]=1.[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([O-:18])=[O:17]>>[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([O-:18])=[O:17]
Reactant: Cc1ccc(S(=O)(=O)O)cc1S(=O)(=O)O
Reactant: O=[N+]([O-])c1ccccc1
Product: O=[N+]([O-])c1ccccc1-c1ccccc1
Yield: 87 %

Procedure:
5 parts of toluene-2,4-disulfonic acid was adsorbed to 6 parts of diatomaceous earth the same as in Example 1 to prepare solid catalyst. The solid catalyst was added to 300 parts of nitrobenzene and heated at a temperature not exceeding 120°C under reduced pressure to remove water as an azeotropic mixture with nitrobenzene. Thus 100 parts of nitrobenzene was distilled off with water. Thereafter, 15 parts of biphenyl was added to the dried mixture and one part of fuming nitric acid was added dropwise with stirring to the mixture cooled to 3° to 5°C in 30 minutes. The nitration reaction and post-treatment were conducted in the same manner as in Example 1, whereby mononitrobiphenyl was obtained with p/o ratio of 1.3. Yield was 87%.
Reaction SMILES: [N:1]([CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:21][CH:20]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[NH2:1][CH2:4][CH2:5][C:6]1([C:11]([NH:13][C@@H:14]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[CH:23][CH:24]=2)[C:15]([OH:17])=[O:16])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: [N-]=[N+]=NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1
Agent: CP(C)C
Solvent: C1CCOC1
Solvent: O
Product: NCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3c(Cl)cccc3Cl)cc2)C(=O)O)CCCC1
Reaction time: 8 h
Yield: 76.6 %

Procedure:
To a solution of (S)-2-[[1-(2-azidoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid (6.28 g, 12.11 mmol) in THF (91 mL) was added a solution of trimethylphosphine in THF (48.5 mL, 48.46 mmol, 1.0M) at 0° C. It was a clear solution in the beginning and after 30 min some precipitate was formed and this mixture was stirred for overnight at which time TLC analysis of the mixture indicated the absence of starting material. Then, 10 equiv. of water (120 mmol, 2.16 mL) was added and the mixture was stirred for 2 h at room temperature. The solvent was removed under vacuum and the residue was azeotrophed two times with toluene to give a pasty material which was purified using HPLC to obtain 4.57 g (77% yield) of (S)-2-[[1-(2-aminoethyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid as an amorphous white solid. ES(+)-HRMS m/e calcd. for C24H27Cl2N3O4 (M+H)+ 492.1452, obsd. 492.1451.