Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]#[N:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>N.CCO.[Ni]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:21][NH2:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCCN(c2ccccc2C#N)CC1
Reactant: [H][H]
Agent: [Ni]
Agent: N
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCCN(c2ccccc2CN)CC1
Reaction time: 2.5 h
Yield: 98.2 %

Procedure:
To a solution of 4-(2-cyano-phenyl)-perhydro-1,4-diazepine-1-carboxylic acid tert-butyl ester (905 mg, 3.0 mmol) in NH3/EtOH (2M, 15 mL) was added Raney Nickel (5 mL slurry in water). The atmosphere was exchanged with hydrogen via balloon and the mixture was allowed to stir for 2.5 h. After this time the mixture was filtered through celite and concentrated to yield the title compound (900 mg). m/z (M+1) 305.31.
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([N:10]2[CH:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:16]3[C:12](=[N:13][N:14](CC4C=CC(OC)=CC=4)[CH:15]=3)[C:11]2=[O:34])[CH:3]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([N:10]2[CH:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:16]3[C:12](=[N:13][NH:14][CH:15]=3)[C:11]2=[O:34])[CH:3]=1
Reactant: COc1ccc(Cn2cc3c(n2)C(=O)N(c2cc(Cl)c(=O)n(C)c2)C3c2ccc(Cl)cc2)cc1
Solvent: CO
Solvent: ClCCl
Product: Cn1cc(N2C(=O)c3n[nH]cc3C2c2ccc(Cl)cc2)cc(Cl)c1=O

Procedure:
The title compound was prepared in analogy to the procedure described in Example 2 using 5-(5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-(4-chlorophenyl)-2-(4-methoxybenzyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one (Step 9.6). tR: 3.39 min (HPLC 1); tR: 0.74 min (LC-MS 2); ESI-MS: 375/377 [M+H]+ (LC-MS 2); Rf=0.30 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 3.44 (s, 3H) 6.19 (s, 1H) 7.24 (d, J=8.6 Hz, 2H) 7.35 (d, J=8.6 Hz, 2H) 7.77-7.85 (m, 1H) 7.89-7.93 (m, 1H) 7.94-7.97 (m, 1H) 13.70 (br. s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5](O)=[N:6][CH:7]=1.P(Br)(Br)[Br:13]>>[Br:13][C:5]1[C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1
Reactant: O=[N+]([O-])c1cc(Br)cnc1O
Reactant: BrP(Br)Br
Product: O=[N+]([O-])c1cc(Br)cnc1Br
Temperature: 0 °C
Reaction time: 1 h
Yield: 43.1 %

Procedure:
77.11 g (354.4 mmol) of 5-bromo-2-hydroxy-3-nitropyridine are heated at 120° C. for 3 hours together with 101.61 g (354.4 mmol) of phosphorus oxytribromide and 33.7 ml (354.4 mmol) of phosphorus tribromide. The reaction mixture is subsequently poured carefully, in small portions, into ice water, stirred for 1 hour and extracted three times with dichloromethane. The organic phase is washed twice with water, dried over sodium sulfate, filtered and freed from the solvent. Chromatographic purification (silica gel/dichloromethane) gives 43.05 g of 2,5-dibromo-3-nitropyridine. ##STR11##
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:15])[CH:12]=2)[CH2:7][NH:6]1)=[O:4].[S]>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([F:15])=[CH:10][CH:9]=2)=[O:4]
Reactant: COC(=O)C1Cc2cc(F)ccc2CN1
Agent: [S]
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc2cc(F)ccc2cn1
Temperature: 150 °C
Reaction time: 16 h

Procedure:
A mixture of 6-fluoro-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid methyl ester (92 g) and sulfur (42 g, 3 equiv.) in xylene (5 L) was stirred at 150° C. for 16 h. The reaction mixture was concentrated, and the resulting residue was dissolved in EtOAc, which was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to give a crude mixture. Purification by flash column chromatography (hexanes/EtOAc, gradient 50%-100%) gave 6-fluoro-isoquinoline-3-carboxylic acid methyl ester as a light yellow solid (27 g, 24% for 3 steps). LRMS (M+H+) m/z 206.1.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:19])[N:8]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:20]=O.[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][C:26](=[O:32])[NH:27]2>>[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[C:25](=[CH:20][C:3]1[NH:4][C:5]3[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]4[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]4)[C:7](=[O:19])[C:6]=3[C:2]=1[CH3:1])[C:26](=[O:32])[NH:27]2
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Reactant: O=C1Cc2c(Br)cccc2N1
Product: Cc1c(C=C2C(=O)Nc3cccc(Br)c32)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Yield: 84.9 %

Procedure:
The title compound was prepared under the same conditions as described in Example 25 with 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-bromo-1,3-dihydro-indol-2-one (prepared according to US20030225127) as starting materials to give 2-(4-bromo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-5-(2-piperidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (58 mg, 84.9%) as a yellow solid.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][OH:6].[Cl-].[OH-].[Na+].O1C[CH2:14][CH2:13][CH2:12]1>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[CH2:14]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:7])[C:13]#[CH:12]
Reactant: C1CCOC1
Reactant: OCCCCCO
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Product: C#CCOCCCCCO
Reaction time: 4 h
Yield: 35 %

Procedure:
First, 65.1 g of 1,5-pentanediol, 18.6 g of proparygyl chloride, 12.0 g of sodium hydroxide (powdery), 5.69 g of benzyltriethylammonium chloride, and 200 ml of tetrahydrofuran were placed in a reaction vessel, and reaction mixture was stirred for 4 hours with heating under reflux. The reaction mixture was filtered through Celite, and the filtrate was poured into water, and extracted twice with diethyl ether. The diethyl ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and concentrated to give a crude product. This crude product was subjected to silica gel chromatography, which afforded 12.4 g (yield, 35%) of 5-(2-propynyloxy)pentanol, nD26.3 1.4533.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2([C:26]#[N:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=1>ClCCl>[CH3:12][S:13]([C:14]1[CH:15]=[CH:16][C:17]([C:20]2([C:26]#[N:27])[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)=[CH:18][CH:19]=1)=[O:9]
Reactant: CSc1ccc(C2(C#N)CCOCC2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)c1ccc(C2(C#N)CCOCC2)cc1
Temperature: 25 °C
Yield: 88.6 %

Procedure:
A solution of meta-chloroperbenzoic acid (5.08 g, 22.66 mmol) in dichloromethane (30 ml) was added dropwise over 15 minutes at 0° C. to a solution of 4-[4-(methylthio)phenyl]tetrahydro-2H-pyran-4-carbonitrile (4.8 g, 20.6 mmol) in dichloromethane (40 ml). The reaction mixture was warmed to room temperature over 4 hours. The mixture was then diluted with dichloromethane (180 ml), washed with sodium sulphite solution and 10% aqueous sodium carbonate. The organic layer was separated, dried over sodium sulphate and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 95:5:0.5 by volume) to provide the title compound (4.55 g, 89%) as an off-white solid. LRMS APCI+ m/z 250 [MH]+.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][NH:17][C:18]([CH3:20])=[O:19])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[NH:21]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C@H:22]([C:31](N[C@@H](C(NCC(O)=O)=O)CCSC)=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1>CN(C=O)C>[NH:21]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C@@H:22]([C:31]([NH:1][CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][NH:17][C:18]([CH3:20])=[O:19])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4])=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CSCC[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C)C(=O)NCC(=O)O
Reactant: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CN
Solvent: CN(C)C=O
Product: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](Cc1ccccc1)NC(=O)OC(C)(C)C

Procedure:
Using H-Gly-Phe-NHNH-COCH3 (0.44 g) and BOC-(D)-Phe-ONB (0.68 g), the desired compound (0.68 g) is obtained in a similar manner to (III) of Example 45, m.p. 208°-209° C., [α]D23 +3.3°(c=0.45, DMF), Rf1 =0.51.
Reaction SMILES: CS(O[N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C@@H:13]2[CH2:17][C@H:16]([S:18][C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][N:14]2[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=2)=[O:39])[CH2:8][CH2:7]1)(=O)=O.[N-:51]=[N+:52]=[N-:53].[Na+]>CN(C)C=O>[N:51]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C@@H:13]2[CH2:17][C@H:16]([S:18][C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][N:14]2[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=2)=[O:39])[CH2:8][CH2:7]1)=[N+:52]=[N-:53]
Reactant: CS(=O)(=O)ON1CCN(C[C@@H]2C[C@H](SC(c3ccccc3)(c3ccccc3)c3ccccc3)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NN1CCN(C[C@@H]2C[C@H](SC(c3ccccc3)(c3ccccc3)c3ccccc3)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 0 °C
Yield: 61.9 %

Procedure:
A solution of (2S,4S)-2-[(4-methanesulfonyloxypiperizin-1-yl)methyl]-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine (4.38 g) and sodium azide (1.19 g) in N,N-dimethylformamide (40 ml) was stirred at 90°-100° C. for 2 hours. The reaction mixture was poured into ice-water (300 ml) and extracted 3 times with saturated aqueous sodium chloride, dried over magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (150 g) eluting with a mixture of dichloromethane and acetone (10:1 V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-2-[(4-azidopiperizin-1-yl)methyl]-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine (2.51 g).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][CH2:13][O:14][C:7]3=[CH:6][C:5]=2[CH2:4][C:3]1=[O:15].[H-].[Na+].F[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N+:25]([O-:27])=[O:26].Cl>CN(C)C=O>[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][CH2:13][O:14][C:7]3=[CH:6][C:5]=2[CH:4]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N+:25]([O-:27])=[O:26])[C:3]1=[O:15]
Reactant: CN1C(=O)Cc2cc3c(cc21)OCCO3
Reactant: O=[N+]([O-])c1ccccc1F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1C(=O)C(c2ccccc2[N+](=O)[O-])c2cc3c(cc21)OCCO3
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 25.1 %

Procedure:
To a stirred solution of 6-methyl-2,3,6,8-tetrahydro-7H-[1,4]dioxino[2,3-f]indol-7-one (1.03 g, 5.01 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (60% w/w dispersion in mineral oil, 0.26 g, 6.5 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, 1-fluoro-2-nitrobenzene (0.70 mL, 6.6 mmol) was added and the mixture was stirred at ambient temperature for 18 h, 10% w/v hydrochloric acid (10 mL) was added at 0° C. and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexanes (1/2) to afford 6-methyl-8-(2-nitrophenyl)-2,3,6,8-tetrahydro-7H-[1,4]dioxino[2,3-f]indol-7-one (0.41 g, 24%): 1H NMR (300 MHz, CDCl3) δ 8.05-8.01 (m, 1H), 7.58-7.51 (m, 1H), 7.49-7.42 (m, 1H), 7.23-7.19 (m, 1H), 6.69 (s, 1H), 6.45 (s, 1H), 5.28 (s, 1H), 4.28-4.18 (m, 4H), 3.21 (s, 3H).
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1([CH3:46])[N:14](COC)[C:13](=[O:18])[C:12]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:25]=[C:26]([CH:37]=[C:38]([O:40][C@H:41]4[CH2:45][CH2:44][O:43][CH2:42]4)[CH:39]=3)[C:27]([NH:29][C:30]3[CH:35]=[N:34][C:33]([CH3:36])=[CH:32][N:31]=3)=[O:28])=[CH:22][C:11]=2[O:10]1>C(Cl)Cl>[CH3:8][C:9]1([CH3:46])[NH:14][C:13](=[O:18])[C:12]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:25]=[C:26]([CH:37]=[C:38]([O:40][C@H:41]4[CH2:45][CH2:44][O:43][CH2:42]4)[CH:39]=3)[C:27]([NH:29][C:30]3[CH:35]=[N:34][C:33]([CH3:36])=[CH:32][N:31]=3)=[O:28])=[CH:22][C:11]=2[O:10]1
Reactant: COCN1C(=O)c2ccc(Oc3cc(O[C@H]4CCOC4)cc(C(=O)Nc4cnc(C)cn4)c3)cc2OC1(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cnc(NC(=O)c2cc(Oc3ccc4c(c3)OC(C)(C)NC4=O)cc(O[C@H]3CCOC3)c2)cn1
Temperature: 25 °C
Reaction time: 48 h
Yield: 28.5 %

Procedure:
Trifluoroacetic acid (1 mL) was added to 3-({2,2-dimethyl-3-[(methyloxy)methyl]-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl}oxy)-N-(5-methylpyrazin-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (54 mg, 0.1 mmol) and stirred at RT for 48 hours. DCM was added and the solvent removed in vacuo. Ethyl acetate (50 mL) was added and the mixture washed with water (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL), dried (MgSO4), and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 0-2.5% methanol in ethyl acetate, to give the desired compound as a white foam (14 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][N:12]=[C:11]([CH2:14][S:15]([C:18]3[CH:26]=[CH:25][C:21]([CH2:22][CH2:23][NH2:24])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[N:10]=2)=[CH:5][CH:4]=1.[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][C:38]([CH:41]([O:44][Si:45]([CH2:50][CH3:51])([CH2:48][CH3:49])[CH2:46][CH3:47])[CH2:42]I)=[CH:37][C:36]=1[NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C>C1COCC1>[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][C:38]([C@@H:41]([O:44][Si:45]([CH2:46][CH3:47])([CH2:48][CH3:49])[CH2:50][CH3:51])[CH2:42][NH:24][CH2:23][CH2:22][C:21]2[CH:20]=[CH:19][C:18]([S:15]([CH2:14][C:11]3[N:10]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)[O:13][N:12]=3)(=[O:16])=[O:17])=[CH:26][CH:25]=2)=[CH:37][C:36]=1[NH:52][S:53]([CH3:56])(=[O:54])=[O:55])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CC[Si](CC)(CC)OC(CI)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Reactant: COc1ccc(-c2nc(CS(=O)(=O)c3ccc(CCN)cc3)no2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)O[C@@H](CNCCc1ccc(S(=O)(=O)Cc2noc(-c3ccc(OC)cc3)n2)cc1)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Yield: 57.3 %

Procedure:
A solution of the amine of Example 17 (0.90 g, 1.78 mmol), 1(S)-(4-benzyloxy-3-(methylsulfonamido)phenyl-1-triethylsiloxy-2-iodoethane (0.665 g, 1.60 mmol) and triethylamine (0.50 mL, 3.56 mmol) in THF (4 mL) was heated at 100° C. in a sealed tube for 60 h. The reaction mixture was cooled and evaporated in vacuo. The residue was flash chromatographed (silica gel; dichloromethane/ethyl ether/methanol: 25/25/0.75) to yield 0.740 g of the title compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[N:5]=[C:4]([NH2:20])[C:3]=1[NH2:21].[C:22]([CH2:26][C:27](Cl)=[O:28])([CH3:25])([CH3:24])[CH3:23]>C(#N)C>[NH2:20][C:4]1[C:3]([NH:21][C:27](=[O:28])[CH2:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[C:2]([CH3:1])[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:18])([F:19])[F:17])=[CH:14][CH:15]=2)[N:5]=1
Reactant: CC(C)(C)CC(=O)Cl
Reactant: Cc1nc(NCc2ccc(C(F)(F)F)cc2)nc(N)c1N
Solvent: CC#N
Product: Cc1nc(NCc2ccc(C(F)(F)F)cc2)nc(N)c1NC(=O)CC(C)(C)C
Reaction time: 0.75 h
Yield: 33.6 %

Procedure:
To a cold stirred solution (ice/water bath) of 6-methyl-N*2*-(4-trifluoromethyl-benzyl)-pyrimidine-2,4,5-triamine (341 mg, 1.15 mmol) in acetonitril (7.5 ml), tert-butylacetyl chloride (0.16 ml, 1.15 mmol) was added dropwise in 2 min. Cold bath was removed and stirring continued for 45 min. The obtained reaction mixture was poured into SCX column (10 g, H+ form), washed with acetonitrile (20 ml), methanol (100 ml), and the product was eluted with 4M NH3 in methanol (60 ml). The volatiles were removed in vacuo and the crude product was purified by flash chromatography on silica gel (20 g) with gradient heptane-ethyl acetate to give 153 mg of solid. Yield 33.7%. LC-MS (m/z) 395.9 (MH+); tR=2.00. 1H NMR (500 MHz, DMSO-d6): 1.02 (s, 9H), 1.96 (s, 3H), 2.15 (s, 2H), 4.5 (d, 2H), 5.9 (br, 2H, NH2), 6.97 (br, 1H, NH), 7.5 (d, 2H), 7.65 (d, 2H), 8.57 (s, 1H, NHCO).
Reaction SMILES: [C:1]1([Te:7][CH2:8][CH2:9][CH:10]2[NH:14]C(=O)N[C:11]2=[O:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:17].[Na+]>>[NH2:14][CH:10]([CH2:9][CH2:8][Te:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:11]([OH:16])=[O:17]
Reactant: O=C1NC(=O)C(CC[Te]c2ccccc2)N1
Reactant: [OH-]
Agent: *C(F)(F)C(*)(F)F
Agent: [Na+]
Product: NC(CC[Te]c1ccccc1)C(=O)O

Procedure:
Reactor produced 123mTe (65.5 mg, 26.3 mCi) was combined with 188.5 mg of carrier Te powder. This material was stirred in tetrahydrofuran (5 ml) to which was added phenyl magnesium chloride (4 mmole) in the same solvent (2 ml). The mixture was stirred rapidly and refluxed but the reaction did not commence as indicated by the absence of the orange-colored product. After the addition of a small crystal of benzoyl peroxide, reaction began immediately. The orange-colored solution was refluxed 1 minute and the reaction flask flushed with O2 and cooled in an ice bath. After warming to room temperature, the solution was stirred 30 minutes, filtered, and the orange-colored filtrate diluted with benzene to a final volume of 25 ml. Aliquots of this solution were counted. The 123mTe-labeled diphenyl ditelluride contained 9.22 mCi of radioactivity. The benzene solution was diluted to 50 ml with methanol and the 123mTe-labeled diphenyl ditelluride reduced with NaBH4 in the manner described in Example IV. To this mixture was added 208 mg, 1 mmole of 5-(beta-bromo ethyl)hydantoin prepared as in Example XI. The mixture was poured into water and extracted with benzene to remove diphenyl ditelluride and other non-polar material. The aqueous layer was acidified to pH 1-2 with 6 N HCl and extracted thoroughly with ether. The combined organic extracts were washed well with water, dried over anhydrous sodium sulfate and the solvent removed in vacuo to give 2.2 mCi of 123mTe-labeled 5-(beta[phenyl telluro]ethyl)hydantoin. This hydantoin is dissolved in 1 N NaOH (2 ml) and heated in a polytetrafluoroethylene-lined bomb by heating at about 165°-167° C. for one hour. Upon cooling, the solution is extracted with benzene and 1 N HCl is added to adjust the pH to 7-8, to provide 123mTe-labeled DL-alpha-amino-gamma-(phenyl telluro)butyric acid.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:28][C@H:27]([CH2:29][N:30]=[N+]=[N-])[O:26][C:25]3=[O:33])=[CH:20][C:19]=2[F:34])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:28][C@H:27]([CH2:29][NH2:30])[O:26][C:25]3=[O:33])=[CH:20][C:19]=2[F:34])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [N-]=[N+]=NC[C@H]1CN(c2ccc(NC3CCN(C(=O)OCc4ccccc4)CC3)c(F)c2)C(=O)O1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: NC[C@H]1CN(c2ccc(NC3CCN(C(=O)OCc4ccccc4)CC3)c(F)c2)C(=O)O1

Procedure:
A solution of 2.51 g (5.35 mmol) 4-[4-{(5R)-5-azidomethyl2-oxo-oxazolidin-3-yl}-2-fluoro-phenylamino]-piperidine-1-carboxylic acid benzyl ester, 1.54 g (5.88 mmol) triphenylphosphine and 964 μl (53.5 mmol) water in 30 ml THF was stirred at 50° C. for 16 h.
Reaction SMILES: C1(C)C=CC=CC=1.[SH:8][CH2:9][C:10]([OH:12])=[O:11].O.[C:14]([OH:18])(=[O:17])[CH:15]=O.O>C1COCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:18]1[C:14](=[O:17])[CH2:15][S:8][CH:9]1[C:10]([OH:12])=[O:11]
Reactant: O=C(O)CS
Reactant: O=CC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Solvent: C1CCOC1
Product: O=C1CSC(C(=O)O)O1
Yield: 74.6 %

Procedure:
Toluene (700 mL), mercaptoacetic acid (38 mL, 50.03 g, 0.543 mol), and p-toluenesulfonic acid (1.0 g) were added to a solution of glyoxylic acid monohydrate (50.0 g, 0.543 mol) in 200 mL of THF in a 2 L round bottom flask equipped with a Dean-Stark trap and condenser. The resultant reaction mixture was refluxed for 3 hours until 24.0 mL of H2O was azeotropically removed. The reaction mixture was cooled, followed by removal of solvent under reduced pressure to yield an off-white solid. This material was purified by recrystallization (hexanes-EtOAc) to give 60.0 g of the product as a crystalline white solid: m.p. 140°-143° C.; 1H NMR (DMSO) δ 3.84 (q, 2H, JAB=16.7 Hz), 6.00 (s, 1H).
Reaction SMILES: [CH:1]1([NH:7][CH2:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[Cl:21][CH2:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl>[CH:1]1([N:7]([CH2:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[S:23]([CH2:22][Cl:21])(=[O:25])=[O:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: c1cncc(CNC2CCCCC2)c1
Reactant: O=S(=O)(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: O=S(=O)(CCl)N(Cc1cccnc1)C1CCCCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A 2.85 g. portion of 3-(cyclohexylaminomethyl)pyridine was dissolved in 20 ml. of dichloromethane, and 2.7 g. of potassium carbonate was added, followed by 3.5 g. of chloromethanesulfonyl chloride. The mixture was stirred at ambient temperature for 2 days, another 2 g. of chloromethanesulfonyl chloride was added, and the mixture was stirred for 3 days more. It was then diluted with 20 ml. of water, and the organic phase was separated, dried over magnesium sulfate and evaporated to an oil. The oil was dissolved in dichloromethane and chromatographed over silica gel, eluting with 9:1 dichloromethane:ethyl acetate. The product-containing fractions were combined and evaporated to obtain 1.4 g. of product, initially an oil, which crystallized spontaneously. M.P. 67°-72°.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15](O)=[O:16])=[CH:6][CH:5]=1)([O-:3])=[O:2].O>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][OH:16])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=C(O)CCCCCc1ccc([N+](=O)[O-])cc1
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(CCCCCCO)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 9.1 g of 6-(4-nitrophenyl)hexanoic acid in 200 ml of dried tetrahydrofuran was added, dropwise, a solution of borane-dimethyl sulfide complex (0.042 mole) in 40 ml of dried tetrahydrofuran. The resulting mixture was stirred at room temperature for 16 hours and then heated at reflux for 1 hour before it was cooled again to room temperature. Water (10 ml) was added, the mixture was stirred for 15 minutes, most of the solvent was removed, and water was added to the residue. The resultant aqueous mixture was extracted with diethyl ether and the extract was washed with aqueous saturated sodium bicarbonate solution, water, and aqueous saturated sodium chloride solution and dried over magnesium sulfate. The solvent was then evaporated to leave 6-(4-nitrophenyl)hexanol as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[C:5]([OH:11])=[N:6][CH:7]=[CH:8][C:9]=1[OH:10])([O-])=O>[Pd].CCOC(C)=O>[NH2:1][C:4]1[C:5]([OH:11])=[N:6][CH:7]=[CH:8][C:9]=1[OH:10]
Reactant: O=[N+]([O-])c1c(O)ccnc1O
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Nc1c(O)ccnc1O
Temperature: 25 °C
Reaction time: 22 h
Yield: 44 %

Procedure:
A mixture of 3-nitropyridine-2,4-diol (1.63 g, 10.44 mmol, Alfa Aesar, Ward Hills, Mass.) and palladium on carbon (10%, wet; 1.2 g, 10 mmol) in EtOAc (52.2 ml) was stirred at RT under H2 (50 psi) for 22 h. The mixture was filtered through a pad of Celite and was washed with MeOH to give 3-aminopyridine-2,4-diol (179b, 44% yield) as a brown, amorphous solid. MS (ESI, pos. ion) m/z: 127.2 (M+1).