Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[F:3][C:4]1([F:8])[CH2:7][NH:6][CH2:5]1.Cl[C:10]1[C:15]([I:16])=[CH:14][N:13]=[CH:12][N:11]=1.CN(C=O)C>C1COCC1.CCOC(C)=O.O>[F:3][C:4]1([F:8])[CH2:7][N:6]([C:10]2[C:15]([I:16])=[CH:14][N:13]=[CH:12][N:11]=2)[CH2:5]1
Reactant: Clc1ncncc1I
Reactant: FC1(F)CNC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: FC1(F)CN(c2ncncc2I)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 40.1 %

Procedure:
To a suspension of sodium hydride (0.062 g, 1.560 mmol) in THF (Volume: 10 mL) was added 3,3-difluoroazetidine (0.097 g, 1.040 mmol) resulting in vigorous gas evolution. After 15 minutes at room temperature, 4-chloro-5-iodopyrimidine (0.25 g, 1.040 mmol) was added as a solution in THF. After 1 h at room temperature, the reaction appeared to have proceeded only about 10%. Next, 5 mL of DMF was added and the reaction mixture was stirred at room temperature overnight. Water was carefully added to quench the reaction, followed by the addition of EtOAc. The mixture was washed once with water and then twice with brine. Next, the mixture was dried over MgSO4, filtered and concentrated to afford a brown solid. The crude material was purified by flash chromatography on silica using an ISCO machine (12 g column, 40 mL/min, 0-8% MeOH in CH2Cl2 over 15 minutes) to give Intermediate 102A (0.125 g, 0.417 mmol, 40.1% yield) as a tan solid.
Reaction SMILES: [CH2:1]([OH:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]Br.[OH-].[Na+]>S(=O)(=O)(O)[O-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:9][CH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: BrCCCCCCBr
Reactant: OCCc1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Product: BrCCCCCCOCCc1ccccc1
Yield: 55.7 %

Procedure:
A mixture of phenethyl alcohol (20 g), 1,6-dibromohexane (195 g) and tetrabutylammonium bisulphate (3.0 g) in 50% w/v NaOH solution (100 ml) was heated at 65°-70° for 4 h. The cooled reaction mixture was poured into H2O (400 ml) and extracted with CX (2×300 ml). The dried extracts were evaporated in vacuo to give a yellow liquid which was purified by distillation under reduced pressure to give the title compound as a colourless liquid (26 g) b.p. 110°/0.1 mm. T.l.c. (EA) Rf 0.62.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:17])[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[CH:11][C:10]([OH:16])=[CH:9][CH:8]=3.O.[CH2:19](Br)[CH2:20][CH2:21][CH3:22]>C(O)(C)C>[CH2:19]([O:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:17])[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[CH:11][C:10]([OH:16])=[CH:9][CH:8]=3)[CH2:20][CH2:21][CH3:22]
Reactant: O=c1c2ccc(O)cc2oc2cc(O)ccc12
Reactant: CCCCBr
Solvent: CC(C)O
Solvent: O
Product: CCCCOc1ccc2c(=O)c3ccc(O)cc3oc2c1
Reaction time: 72 h

Procedure:
3,6-Dihydroxy xanthone (1,60.7 mmol) was dissolved into hot basic water (Na2CO3 240 mmol in 600 ml water). After the 3,6-dihydroxy xanthone was completely dissolved, the temperature was controlled to 70° C. Isopropyl alcohol (10 ml) was added to the reaction mixture and butyl bromide (180 mmol) was added dropwise. The reaction mixture was stirred rigorously for 72 hours. A white precipitate appeared which was then filtered and washed with water. There was almost no disubstituted compound in the product. This precipitate was dissolved in 3% NaOH, filtered and finally reprecipitated with HCl yielding 90% of 3-butoxy-6-hydroxy xanthone.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH2:35]([N:37]([CH2:41][CH3:42])[CH2:38][C:39]#[CH:40])[CH3:36]>>[Cl:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:40]#[C:39][CH2:38][N:37]([CH2:41][CH3:42])[CH2:35][CH3:36])[S:17][C:10]=12
Reactant: NC(=O)C1(C(=O)N(c2ccc(F)cc2)c2ccc(Oc3ccnc4cc(I)sc34)c(Cl)c2)CC1
Reactant: C#CCN(CC)CC
Product: CCN(CC)CC#Cc1cc2nccc(Oc3ccc(N(C(=O)C4(C(N)=O)CC4)c4ccc(F)cc4)cc3Cl)c2s1
Yield: 28.7 %

Procedure:
Prepared from N-(3-chloro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl) -N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.160 g, 0.132 mmol), and N, N-diethylprop-2-yn-1-amine (0.0132 g, 0.118 mmol) according to the procedure for Example 6, Step B. The product was purified by Horizon reverse phase using Biotage 12M C18 column. The crude was loaded to the samplet with EtOAc and dried under vacuum. The product was eluted with 55-75% acetonitrile in water and was obtained as a white powder (20 mg, 26%). 1H NMR (CDCl3, 400 MHz) δ 10.14 (s, 1H), 8.50 (s, 1H), 8.46 (d, J=5.5 Hz, 1H), 7.90 (s, 1H), 7.54 (s, 1H), 7.46 (m, 3H), 7.20 (d, J=8.6 Hz, 1H), 7.05 (t, J=8.8 Hz, 2H), 6.42 (d, J=5.5 Hz, 1H), 3.71 (s, 2H), 2.65 (q, J=7, 14 Hz, 4H), 1.77 (m, 4H), 1.13 (t, J=7.2 Hz, 6H). LRMS (ESI pos) m/e 591 (M+1).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:5])[CH3:4].Cl[C:7]1[CH:12]=[CH:11][N+:10]([O-:13])=[C:9]([CH3:14])[C:8]=1[CH3:15]>CS(C)=O.O>[CH2:3]([O:5][C:7]1[CH:12]=[CH:11][N+:10]([O-:13])=[C:9]([CH3:14])[C:8]=1[CH3:15])[CH3:4]
Reactant: CCO
Reactant: Cc1c(Cl)cc[n+]([O-])c1C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCOc1cc[n+]([O-])c(C)c1C
Temperature: 30 °C
Reaction time: 8 h
Yield: 127 %

Procedure:
To a solution prepared by diluting 8.6 g (2.0 eq.) of 60% sodium hydride with 200 mL of dimethylsulfoxide, 9.9 g (2.0 eq.) of anhydrous ethanol was added, and the mixture was allowed to react for one hour at 60° C. The reaction liquid was cooled to 30° C., and then a liquid containing 17.0 g of 4-chlor-2,3-dimethylpyridine-1-oxide dissolved in dimethylsulfoxide (70 mL) was added dropwise. The mixture was allowed to react for 2 hours at 40 to 50° C., and then was left to stand overnight at room temperature. 16 mL of water was added to the reaction liquid, and the mixture was concentrated, to obtain a residue in the form of a black paste. Subsequently, the residue was dissolved in 500 mL of water, and then the aqueous solution was extracted three times with 670 mL of chloroform. The extract was dried over anhydrous magnesium sulfate, and then was concentrated to dryness under reduced pressure. The obtained residue was purified on a silica gel column, to obtain 22.9 g of 4-ethoxy-2,3-dimethylpyridine-1-oxide.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([NH:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:9]([OH:12])[CH2:10][F:11])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl.CCOC(C)=O>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([NH:13][C:14](=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:9](=[O:12])[CH2:10][F:11])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(NC(=O)c1ccccc1)C(O)CF
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CC(NC(=O)c1ccccc1)C(=O)CF
Yield: 95 %

Procedure:
1,1,1-Triacetoxy-1,1-dihydro-1,2-benzodioxol-3(1H)-one (273 mg, 0.64 mmol) was added in one portion to a stirred solution of 3-benzoylamino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (100 mg, 0.32 mmol) (prepared from benzoic acid and 3-amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester using standard coupling procedures eg. HOBT, DMAP, and EDC) in dry dichloromethane (DCM) (2 ml) at 0° C. The mixture was brought to room temperature (r.t.) during 16 h, diluted with EtOAc, then poured into a 1:1 mixture of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulphate. The organic layer was removed and the aqueous layer re-extracted with EtOAc. The combined organic organic extracts were dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (30% EtOAc in hexane) to afford the title compound as a colourless gum (94 mg, 95%): 1H NMR (CDCl3) δ 7.80 (2H, m), 7.50 (4H, m), 5.2 (3H, m), 2.95 (2H, m), 1.45 (9H, s); 13C NMR (CDCl3) δ 203.19, 203.02, 171.02, 167.57, 133.54, 133.04, 132.60, 129.16, 127.97, 127.53, 85.52, 83.70, 82.80, 53.13, 53.03, 36.63, 36.61, 28.44, 28.37; 19F NMR (CDCl3) δ −232.09(t, J 49 Hz).
Reaction SMILES: [C:1]1([NH:7][C:8]2[C:16]3[C:15]4[CH2:17][NH:18][CH2:19][CH2:20][C:14]=4[NH:13][C:12]=3[N:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:21][C:22]1[CH:23]=[C:24]([S:28](Cl)(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1.C(N(CC)CC)C>ClCCCl>[Cl:21][C:22]1[CH:23]=[C:24]([S:28]([N:18]2[CH2:19][CH2:20][C:14]3[NH:13][C:12]4[N:11]=[CH:10][CH:9]=[C:8]([NH:7][C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:16]=4[C:15]=3[CH2:17]2)(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1
Reactant: c1ccc(Nc2ccnc3[nH]c4c(c23)CNCC4)cc1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(c1cccc(Cl)c1)N1CCc2[nH]c3nccc(Nc4ccccc4)c3c2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 22.8 %

Procedure:
Phenyl-(6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrol-4-yl)-amine (40 mg, 0.15 mmol), 3-chlorophenylsulfonyl chloride (38 mg, 0.18 mmol), and triethylamine (0.06 mL, 0.45 mmol) were dissolved in 1,2-dichloroethane (2.0 mL), and stirred overnight at room temperature. The reaction mixture was added directly to a Biotage column. The crude product was purified via Biotage eluting with CH2Cl2/MeOH (9/1, v/v) to provide 11 (15 mg, 23% yield) as a brown solid. LC-MS (M+H=439, obsd.=439).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]2[CH2:6][O:7][B:8]([OH:9])[C:4]=2[CH:3]=1.[H-].[Na+].Br[CH:15]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17].Cl>CN(C=O)C>[CH2:19]([O:18][C:16](=[O:17])[CH:15]([O:1][C:2]1[CH:11]=[CH:10][C:5]2[CH2:6][O:7][B:8]([OH:9])[C:4]=2[CH:3]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20]
Reactant: CCOC(=O)C(Br)c1ccccc1
Reactant: OB1OCc2ccc(O)cc21
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(Oc1ccc2c(c1)B(O)OC2)c1ccccc1
Temperature: 0 °C
Reaction time: 24 h
Yield: 59.7 %

Procedure:
H181 (110 mg, 0.73 mmol) was dissolved in DMF (6.0 mL) and cooled to 0° C. with ice bath. To this solution under nitrogen were added in sequence NaH (60% in mineral oil, 117 mg, 2.93 mmol) and ethyl 2-bromo-2-phenylacetate (0.51 mL, 2.93 mmol). The reaction mixture was stirred for 1 d then treated with 1.0 M HCl (10.0 mL). After extraction with ethyl acetate, the organic layer was washed with water and brine, and dried over anhydrous Na2SO4. The residue after rotary evaporation was purified by column chromatography over silica gel to give the title compound (136 mg, 60% yield). 1H NMR (300 MHz, CDCl3): δ 7.62-7.56 (m, 2H), 7.44-7.12 (m, 6H), 5.67 (s, 1H), 5.03 (s, 2H), 4.30-4.10 (m, 2H) and 1.20 (t, J=7.2 Hz, 3H) ppm; Mp: 94-97° C.
Reaction SMILES: C([O:3][C:4](=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[N:16]=2)=[O:14])[CH:7]=1)C.[Cl:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1>>[Cl:23][C:24]1[CH:29]=[C:28]([C:17]2[N:16]=[C:15]([C:13]([NH:12][C:8]3[CH:7]=[C:6]([CH2:5][C:4]([OH:3])=[O:22])[CH:11]=[CH:10][CH:9]=3)=[O:14])[CH:20]=[CH:19][CH:18]=2)[CH:27]=[CH:26][CH:25]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: CCOC(=O)Cc1cccc(NC(=O)c2cccc(Br)n2)c1
Product: O=C(O)Cc1cccc(NC(=O)c2cccc(-c3cccc(Cl)c3)n2)c1

Procedure:
The pyridyl bromide (77) (44 mg, 0.12 mmol) was coupled to 3-chloro-phenylboronic acid (20 mg, 0.13 mmol) using Method E. During this reaction, hydrolysis occurred. The residue was extracted using Work-up E1 to give the acid. The solid was further purified by preparative HPLC to give the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3[N:16]=[C:17](/[CH:19]=[CH:20]/[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:18][C:12]=3[CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>[Pd].CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3[N:16]=[C:17]([CH2:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[O:18][C:12]=3[CH2:11]2)=[O:9])=[CH:6][CH:7]=1
Reactant: O=C(c1ccc(F)cc1)N1CCc2nc(/C=C/c3ccccc3)oc2C1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: O=C(c1ccc(F)cc1)N1CCc2nc(CCc3ccccc3)oc2C1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
10% Palladium on charcoal (15 mg, 0.0144 mmol) was added to a stirred suspension of 5-[(4-fluorophenyl)carbonyl]-2-[(E)-2-phenylethenyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (0.05 g, 0.144 mmol) and ammonium formate (54 mg, 0.86 mmol) in MeOH (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 100° C. for 1 hour. The mixture was filtered through a pad of diatomaceous earth and washed with DCM. The filtrate was treated with a saturated solution of sodium chloride and extracted with more DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-[(4-fluorophenyl)carbonyl]-2-(2-phenylethyl)-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine as a colourless oil.
Reaction SMILES: C(C(C(C([O-])=O)O)O)([O-])=O.[CH2:11]([N:18]=[C:19]=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N=C=S)C1C=CC=CC=1.[CH:31]1([CH2:34][N:35]2[CH2:53][CH2:52][C@:42]34[C:43]5[C:44]6[O:51][C@H:41]3[C@H:40]([NH:54][CH3:55])[CH2:39][CH2:38][C@@:37]4([OH:56])[C@H:36]2[CH2:49][C:48]=5[CH:47]=[CH:46][C:45]=6[OH:50])[CH2:33][CH2:32]1>>[CH:31]1([CH2:34][N:35]2[CH2:53][CH2:52][C@:42]34[C:43]5[C:44]6[O:51][C@H:41]3[C@@H:40]([N:54]([CH3:55])[C:19]([NH:18][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:20])[CH2:39][CH2:38][C@@:37]4([OH:56])[C@H:36]2[CH2:49][C:48]=5[CH:47]=[CH:46][C:45]=6[OH:50])[CH2:32][CH2:33]1
Reactant: CN[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
Reactant: O=C=NCc1ccccc1
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: S=C=NCc1ccccc1
Product: CN(C(=O)NCc1ccccc1)[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5

Procedure:
tartrate 132 (yield: 65%), 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(N-methyl-N′-benzylthioureido)morphinan.tartrate 133 (yield: 88%) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(N-methyl-N′-benzylthioureido)morphinan.tartrate 134 (yield: 74%) were obtained by following the procedure of example 121 but using benzylisocyanate and benzylisothiocyanate instead of 3,4-dichlorophenylisocyanate, and using 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-methylaminomorphinan 10 instead of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-methylaminomorphinan 4.
Reaction SMILES: [C:1]1([CH2:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[CH:24](N(C)C)[N:25](C)C)(C)(C)C.Cl.NO.C([O-])(=O)C.[Na+].C([O-])(O)=O.[Na+]>C1COCC1>[C:1]1([C:7]2[CH:24]=[N:25][O:9][C:8]=2[C:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Reactant: O=C(Cc1ccccc1)c1c[nH]c2ncccc12
Agent: CC(=O)[O-]
Agent: Cl
Agent: NO
Solvent: C1CCOC1
Product: c1ccc(-c2cnoc2-c2c[nH]c3ncccc23)cc1
Temperature: 60 °C
Yield: 58.8 %

Procedure:
To a solution of 2-phenyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone (200 mg, 0.85 mmol) in dry THF (5 mL) was added tert-butoxy-N,N,N′,N′-tetramethyl-methanediamine (Bredereck's reagent) (440 mg, 2.52 mmol). The solution was heated at 60° C. for 3 h and evaporated to dry. The resulting residue was dissolved in ethanol (5 mL). To this ethanol solution was then added hydroxylamine hydrochloride (300 mg, 4.32 mmol) and sodium acetate (420 mg, 5.12 mmol). The mixture was heated under reflux for 10 h, cooled, and poured into aqueous NaHCO3 solution. The crude product was collected by filtration and washed with water. After purification by Gilson HPLC, the pure product was obtained as powder (130 mg, 0.50 mmol, 59%).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:26])=[C:7]([N:9]2[C:13](=[O:14])[NH:12][C:11]([C:15]3[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH:23]4[CH2:25][CH2:24]4)=[CH:17][CH:16]=3)=[N:10]2)[CH:8]=1.C[O:28][CH2:29][C:30]([CH3:35])([CH3:34])[C:31](O)=[O:32].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[Cl:26][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:29](=[O:28])[C:30]([CH3:35])([CH3:34])[CH2:31][OH:32])=[CH:8][C:7]=1[N:9]1[C:13](=[O:14])[NH:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH:23]3[CH2:25][CH2:24]3)=[CH:17][CH:16]=2)=[N:10]1
Reactant: COCC(C)(C)C(=O)O
Reactant: NCc1ccc(Cl)c(-n2nc(-c3ccc(C#CC4CC4)cc3)[nH]c2=O)c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CC(C)(CO)C(=O)NCc1ccc(Cl)c(-n2nc(-c3ccc(C#CC4CC4)cc3)[nH]c2=O)c1
Yield: 9.4 %

Procedure:
The title compound was prepared according to the procedure described in Example-107 by using 1-(5-(aminomethyl)-2-chlorophenyl)-3-(4-(cyclopropylethynyl)phenyl)-1H-1,2,4-triazol-5(4H)-one (0.080 g, 0.228 mmol), DMF (5 mL), 3-methoxy-2,2-dimethylpropanoic acid (0.040 g, 0.342 mmol), BOP (0.151 g, 0.342 mmol), TEA (2.0 mL) to afford 0.010 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 0.75 (m, 2H), 0.83 (m, 2H), 1.10 (s, 6H), 1.51 (m, 1H), 3.34 (m 2H), 4.31 (br s, 2H), 4.85 (m, 1H), 7.37-7.50 (m, 3H), 7.58 (d, J=7.8 Hz, 1H), 7.77-7.83 (m, 3H), 8.11 (br s, 1H), 12.56 (s, 1H); MS (m/z): 465.07 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]([NH:4][C:5]([CH:7]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:8]1)=[O:6])[CH3:3].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1.[H-].[Na+].C1OCCOCCOCCOCCOCCOC1>C(#N)C>[OH:8][CH:7]([CH:9]([O:23][C:20]1[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:5]([NH:4][CH:2]([CH3:1])[CH3:3])=[O:6]
Reactant: Oc1ccc(Cl)cc1
Reactant: CC(C)NC(=O)C1OC1c1ccccc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: CC(C)NC(=O)C(O)C(Oc1ccc(Cl)cc1)c1ccccc1

Procedure:
This compound was prepared from N-(1-methylethyl)-3-phenyl-2-oxiranecarboxamide (6.16 g.) p-chlorophenol (3.9 g.), sodium hydride (50% oil dispersion, 1.5 g.) 18-crown-6 (0.9 g.), and acetonitrile (250 ml.) as described in Example 12. The product melted at 148°-150°, and amounted to 2.7 g.
Reaction SMILES: [Cl:1][C:2]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:3]=1[O:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[C:11]([N+:23]([O-])=O)[CH:10]=1)=[O:7]>[Ni]>[NH2:23][C:11]1[CH:10]=[C:9]([NH:8][C:6](=[O:7])[CH2:5][O:4][C:3]2[CH:26]=[CH:27][C:28]([C:30]([F:31])([F:32])[F:33])=[CH:29][C:2]=2[Cl:1])[CH:14]=[CH:13][C:12]=1[O:15][CH2:16][CH2:17][N:18]([CH2:19][CH3:20])[CH2:21][CH3:22]
Reactant: CCN(CC)CCOc1ccc(NC(=O)COc2ccc(C(F)(F)F)cc2Cl)cc1[N+](=O)[O-]
Agent: [Ni]
Product: CCN(CC)CCOc1ccc(NC(=O)COc2ccc(C(F)(F)F)cc2Cl)cc1N

Procedure:
A suspension of 330 mg (0.674 mmol) 2-(2-chloro-4-trifluoromethyl-phenoxy)-N-[4-(2-diethylamino-ethoxy)-3-nitro-phenyl]-acetamide (Example 160) and 200 mg Raney nickel was hydrogenated at RT and 3 bar. The catalyst was filtered off and the filtrate evaporated down i. vac.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1>C(Cl)Cl>[CH3:9][NH:1][CH2:2][CH2:3][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: c1ccc2[nH]ccc2c1
Solvent: ClCCl
Product: CNCCc1c[nH]c2ccccc12

Procedure:
IR-spectrum (methylene chloride): 3490 cm-1 (indole).
Reaction SMILES: [C:1]12[CH:24]=[C:22]3[N:23]=[C:19]([CH:20]=[CH:21]3)[CH:18]=[C:16]3[NH:17][C:13]([CH:14]=[CH:15]3)=[CH:12][C:10]3=[N:11][C:7]([CH:8]=[CH:9]3)=[CH:6][C:4]([NH:5]1)=[CH:3][CH:2]=2.CC([O-])=O.CC([O-])=O.[Cu+2:33].O>CO>[C:1]12[CH:24]=[C:22]3[N:23]=[C:19]([CH:20]=[CH:21]3)[CH:18]=[C:16]3[NH:17][C:13]([CH:14]=[CH:15]3)=[CH:12][C:10]3=[N:11][C:7]([CH:8]=[CH:9]3)=[CH:6][C:4]([NH:5]1)=[CH:3][CH:2]=2.[Cu:33]
Reactant: [Cu+2]
Agent: C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3
Agent: CC(=O)[O-]
Solvent: CO
Solvent: O
Product: [Cu]
Reaction time: 0.33 h

Procedure:
A 1:1.1 molar solution of porphyrin compound (VIII) (50 milligrams, 36.5 millimoles) to Cu(OAc)2.H2O (8 milligrams, 40 millimoles) to Cu(OAc)2H2O was prepared by dissolving the two compounds in methanol. The resulting purple solution was stirred for 20 minutes during which time the color turned to red. The solvent was then removed by rotary evaporation. The resulting residue was dissolved in dichloromethane to make an organic phase, which was washed with water and then dried over anhydrous sodium sulfate. The solvent of the organic phase was removed by rotary evaporation, leaving a red copper porphyrin compound. The compound was re-dissolved in dichloromethane and purified on a silica pad eluting with a 3:1:1 solvent mixture of hexane to dichloromethane to acetone. The solvent of the organic phase was removed by rotary evaporation, leaving 36 milligrams of the copper porphyrin compound (IX) (70% yield).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:12]=[C:11]([CH2:26][CH:27]=[O:28])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>ClCCl>[CH2:1]([NH:8][C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:12]=[C:11]([CH2:26][CH2:27][OH:28])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=CCc1cc(NCc2ccccc2)c([N+](=O)[O-])c(NCc2ccccc2)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Product: O=[N+]([O-])c1c(NCc2ccccc2)cc(CCO)nc1NCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 53.7 %

Procedure:
(4,6-Bis-benzylamino-5-nitro-pyridin-2-yl)-acetaldehyde (250 mg, 0.66 mmol) was stirred in 15 ml dichloromethane. Sodium borohydride (38 mg, 0.99 mmol) was added and the solution stirred at ambient temperature overnight. The reaction mixture was partitioned between DCM and water, the organics dried over magnesium sulphate and concentrated to give a crude solid which was purified by column chromatography on silica, eluting with pentane:EtOAc, 4:1 to 1:1 to afford the title compound as a yellow solid, (134 mg, 53%).
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].[NH2:19][C@H:20]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Br:32])[CH:27]=1)[C@H:21]([OH:25])[C:22]([OH:24])=[O:23].O1CCOCC1>O>[Br:32][C:28]1[CH:27]=[C:26]([C@@H:20]2[C@@H:21]([C:22]([OH:24])=[O:23])[O:25][C:2](=[O:4])[NH:19]2)[CH:31]=[CH:30][CH:29]=1
Reactant: N[C@H](c1cccc(Br)c1)[C@H](O)C(=O)O
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: O=C1N[C@H](c2cccc(Br)c2)[C@@H](C(=O)O)O1
Reaction time: 0.25 h
Yield: 61 %

Procedure:
To triphosgene (36.5 mg, 0.123 mmol) and Na2CO3 (65.2 mg, 0.615 mmol) in Water (2.000 mL) at 0° C. was added dropwise a solution of (2S,3R)-3-amino-3-(3-bromophenyl)-2-hydroxypropanoic acid (20 mg, 0.077 mmol) in Water (0.5 mL)/1,4-Dioxane (0.5 mL). After 15 min, the ice bath was removed and stirring was continued for one hour. ethylacetate (1 ml) was added to the reaction mixture and after five minutes the ethylacetate layer was discarded and the aqueous layer was acidified to pH 2 and extracted with ethylacetate (5 mL×3). The combined organics were dried over magnesium sulfate, filtered and concentrated providing (4R,5S)-4-(3-bromophenyl)-2-oxooxazolidine-5-carboxylic acid (14.2 mg, 0.047 mmol, 61.3% yield) as a white solid. Mass spec.: 287.79 (MH)+.