Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:15][C:16](C)(C)C)=[O:14])=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].S(Cl)(Cl)=O.[CH3:24]O>>[NH2:1][C@H:2]([C:3]([O:5][CH3:24])=[O:4])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:9][CH:8]=1
Reactant: CO
Reactant: CC(C)(C)OC(=O)c1ccc(C[C@H](N)C(=O)O)cc1
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(C[C@H](N)C(=O)OC)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
To a solution of (S)-2-amino-3-(4-(tert-butoxycarbonyl)phenyl)propanoic acid (500.0 mg, 1.88 mmol) in MeOH (20 mL) at 0° C. was slowly added thionyl chloride (447.64 mg, 3.77 mmol). The reaction was stirred for 1 h at 0° C. then warmed to RT and stirred for 1 h. The solvent was removed under reduced pressure. The reaction mixture was washed with saturated aqueous NaHCO3 (20 ml) and extracted with DCM (3×10 ml). The organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (EA/hexanes) to afford 425 mg (95%) of (S)-methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate as the HCl salt. LCMS-ESI (m/z) calculated for C12H15NO4: 237.1; found 238.0 [M+H]+, tR=1.01 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 3H), 7.94 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.3 Hz, 2H), 4.37 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 3.68 (s, 3H), 3.20 (dd, J=11.8, 6.8 Hz, 2H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([N:24]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:12]1=2.B1([C:48]2[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH:49]=2)OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:24]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[S:21]([C:18]2[CH:19]=[CH:20][C:12]3[N:11]([C:3]4[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=4[C:48]4[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH:49]=4)[CH2:16][CH2:15][O:14][C:13]=3[CH:17]=2)(=[O:23])=[O:22])=[CH:36][CH:35]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccc([N+](=O)[O-])cc2Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccc([N+](=O)[O-])cc2C2=CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 100 °C

Procedure:
A microwave vial was charged with 4-(2-bromo-4-nitrophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.136 g, 0.220 mmol) (STEP 1, EXAMPLE 64), 3,6-dihydro-2h-pyridine-1-N-boc-4-boronic acid pinacol ester (0.136 g, 0.440 mmol), tetrakis(triphenylphosphine)palladium(0) (0.025 g, 0.022 mmol), and K2CO3 (0.152 g, 1.101 mmol). The solids were diluted with dioxane (1.468 mL) and water (0.734 mL), and the reaction was heated under microwave irradiation at 100° C. for 30 minutes. The reaction was diluted with water and DCM, the layers separated. The aqueous was washed once more with DCM, and the organics were combined and dried using a phase separator to yield material. After concentration under a vacuum, the material was taken up in methanol (and a small amount of DCM) and purified via 5 g SCX column to provide tert-butyl 4-(2-(7-(N-(4-methoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate, which was taken forward without further purification. m/z (ESI) 720.0 (M+H)+.
Reaction SMILES: [CH3:1][C@@H:2]1[C@:26]2([O:32][CH2:31][C@H:29]([CH3:30])[CH2:28][CH2:27]2)[O:25][C@H:4]2[CH2:5][C@@H:6]3[C@@:20]([CH3:21])([C@@H:3]12)[C@H:19]([OH:22])[C:18](=[O:23])[C@H:17]1[C@H:7]3[CH2:8][CH2:9][C@@H:10]2[C@:15]1([CH3:16])[CH2:14][CH2:13][C@H:12]([OH:24])[CH2:11]2.[C:33]([Si:37]([CH3:40])([CH3:39])Cl)([CH3:36])([CH3:35])[CH3:34].N1C=CN=C1>CN(C=O)C>[Si:37]([O:24][C@H:12]1[CH2:13][CH2:14][C@@:15]2([CH3:16])[C@@H:10]([CH2:9][CH2:8][C@@H:7]3[C@@H:17]2[C:18](=[O:23])[C@@H:19]([OH:22])[C@@:20]2([CH3:21])[C@H:6]3[CH2:5][C@@H:4]3[O:25][C@@:26]4([O:32][CH2:31][C@H:29]([CH3:30])[CH2:28][CH2:27]4)[C@@H:2]([CH3:1])[C@@H:3]32)[CH2:11]1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:40])[CH3:39]
Reactant: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O)CC[C@]5(C)[C@H]4C(=O)[C@@H](O)[C@]3(C)[C@H]1[C@@H]2C
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@]5(C)[C@H]4C(=O)[C@@H](O)[C@]3(C)[C@H]1[C@@H]2C

Procedure:
Using the procedure described in J. Am. Chem. Soc., 1972,94, 6190, (3β,5α,12β,25R)-spirostan-3,12-diol-11-one (see preparation G6) was silylated with t-butyldimethylchlorosilane and imidazole in DMF to give the title compound.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[C:16]4=[N:17][C:18]([C:21](=O)[CH3:22])=[CH:19][N:20]=[C:15]4[N:14]=[N:13]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[O:24]1[CH2:27][CH:26]([O:28][NH2:29])[CH2:25]1>>[O:24]1[CH2:27][CH:26]([O:28]/[N:29]=[C:21](/[C:18]2[N:17]=[C:16]3[N:12]([CH2:11][C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[N:1]=[CH:2][CH:3]=[CH:4]5)[N:13]=[N:14][C:15]3=[N:20][CH:19]=2)\[CH3:22])[CH2:25]1
Reactant: CC(=O)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Reactant: NOC1COC1
Product: C/C(=N\OC1COC1)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Yield: 23 %

Procedure:
The title compound was prepared from 1-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)ethanone (22.4) and O-(oxetan-3-yl)hydroxylamine (intermediate U) in 23% yield using the same procedure as described in the synthesis of example 22. 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.27 (s, 1H), 8.89 (m, 1H), 8.35 (d, 1H), 8.01 (m, 2H), 7.82 (m, 1H), 7.52 (dd, 1H), 6.22 (s, 2H), 5.45 (t, 1H), 4.86 (t, 2H), 4.66 (m, 2H), 2.40 (s, 3H). LCMS (method B): [MH]+=376, tR=2.26 min.
Reaction SMILES: [CH:1]([OH:3])=O.[NH2:4][C:5]1[C:12]([N+:13]([O-])=O)=[C:11]([CH3:16])[C:10]([N+:17]([O-])=O)=[CH:9][C:6]=1[C:7]#[N:8].N[C:21]1C([N+]([O-])=O)=C(C)C([N+]([O-])=O)=CC=1C#N.O.C(O)=O>[Pt].O>[CH:1]([NH:17][C:10]1[CH:9]=[C:6]([C:7]#[N:8])[C:5]2[N:4]=[CH:21][NH:13][C:12]=2[C:11]=1[CH3:16])=[O:3]
Reactant: Cc1c([N+](=O)[O-])cc(C#N)c(N)c1[N+](=O)[O-]
Reactant: O=CO
Agent: [Pt]
Solvent: O
Product: Cc1c(NC=O)cc(C#N)c2nc[nH]c12
Temperature: 95 °C
Reaction time: 0.5 h
Yield: 65 %

Procedure:
A mixture of platinum on carbon (sulfided) catalyst (5.3 kg of Engelhard C3759), formic acid (86.8 kg) and water (28.4 L) is heated to about 95° C. A mixture of 2-amino-4-methyl-3,5-dinitrobenzonitrile (5) (10.9 kg), formic acid (28 kg) and water (8 L) is then added to the catalyst-containing solution over about 45 minutes, while maintaining the temperature of the catalyst-containing mixture at about 95° C. The vessel that formerly contained the initial 2-amino-4-methyl-3,5-dinitrobenzonitrile/water/formic acid mixture is then rinsed with water (5.5 L) and the rinse solution is added to the catalyst-containing mixture. The resultant catalyst-containing mixture is then agitated at about 95° C. for about 30 minutes. After the mixture is cooled to about 35-45° C., the mixture is filtered to remove the catalyst and the filtered catalyst is washed with 96% formic acid (32.3 kg). The combined product-containing filtrate is placed under vacuum and heated (from about 25° C. to about 60° C.), and formic acid/water is distilled off, until about 98.4 kg of distillate is collected. At this point, methanol (109.1 kg) is added to the product-containing mixture. The mixture is gradually cooled to about 5° C., over a period of about 1 hour, and held at this temperature for about 1 hour. The mixture is then filtered and the product filter cake is washed with methanol (42.5 kg). The product is then dried in a vacuum tray dryer, at a temperature of about 45-50° C. and a vacuum of about 70 torr until dry to obtain 6-(Formylamino)-7-methyl-1H-benzimidazole-4-carbonitrile (9) (6.4 kg, 65% yield).
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:9]([O:11]C)=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].Cl>C1COCC1>[C:1]([O:5][C:6]([C@@H:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:16][CH:15]=1)[C:9]([OH:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)OC(C)(C)C
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)[C@@H](Cc1ccc(C(F)(F)F)cc1)C(=O)O
Temperature: 0 °C

Procedure:
(S)-Methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate (6.20 g, 17.9 mmol) was dissolved in THF (180 mL) and cooled to 0° C. A 0.2 M of aq. LiOH (89.3 ml, 17.9 mmol) was added dropwise and stirred 20 minutes before TLC analysis (2:1 Hexanes/EtOAc) showed no starting material. The PH of the reaction was carefully adjusted to PH=8 with 1 N HCl. The aqueous layer was washed with diethyl ether and the organics were back extracted with 1% aqueous sodium bicarbonate and the combined aqueous layers were carefully brought to a PH=4 and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to afford (S)-2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoic acid, which was used without further purification.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][N:4]1[CH2:13][CH2:14][OH:15].[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[C:21](Cl)=[O:22]>N1C=CC=CC=1>[CH3:30][O:29][C:25]1[CH:24]=[C:20]([CH:19]=[C:18]([O:17][CH3:16])[C:26]=1[O:27][CH3:28])[C:21]([NH:1][CH2:2][CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][N:4]1[CH2:13][CH2:14][OH:15])=[O:22]
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Reactant: NCC1c2ccccc2CCN1CCO
Solvent: c1ccncc1
Product: COc1cc(C(=O)NCC2c3ccccc3CCN2CCO)cc(OC)c1OC
Reaction time: 8 h

Procedure:
A solution of 20.6 g. of 1-aminomethyl-2-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline and 27.6 g. of 3,4,5-trimethoxybenzoyl chloride in 130 ml. of pyridine is left to stand overnight. The thus-precipitated 1-(3,4,5-trimethoxybenzamidomethyl)-2-[2-(3,4,5-trimethoxybenzoyloxy)-ethyl]-1,2,3,4-tetrahydroisoquinoline is filtered, washed with ether, and extracted with methanol; m.p. 236°-238°. The pyridine filtrate is evaporated, the residue is taken up in chloroform and washed several times with 5% potassium bicarbonate solution. After drying and evaporation, 1-(3,4,5-trimethoxybenzamidomethyl)-2-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline is obtained in this way; m.p. 138°-140° (from ethyl acetate).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[CH:5][NH:6][CH:7]=1.[NH2:8][C:9](N)=[S:10].ClC1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15]N=1.[OH-].[Na+]>C(O)C.O>[NH:6]1[CH:7]=[C:3]([CH2:2][S:10][C:9]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][N:8]=2)[N:4]=[CH:5]1
Reactant: ClCc1c[nH]cn1
Reactant: NC(N)=S
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=[N+]([O-])c1ccc(SCc2c[nH]cn2)nc1
Temperature: 21 °C
Reaction time: 3 h

Procedure:
A mixture of 0.6 g (3.9 mmol) of 4-chloromethylimidazole and of an equimolar equivalent of thiourea (0.3 g) in 10 ml of ethanol is brought to reflux for 30 min. 5 ml of ethanol, 20 ml of water and 1.2 molar equivalents of 2-chloro-5-nitropyridine (0.74 g) in 5 ml of hot ethanol are added to this mixture. The light solution is cooled to 0°-10° C. in an ice bath and a solution of 0.49 g of sodium hydroxide in 10 ml of water is added dropwise under nitrogen at 0°-10° C. and then the mixture is stirred for a further 3 h at 21° C. The precipitate is collected, washed with water and chromatographed through silica gel with a mixture of chloroform and methanol (1-20%) to give the title compound, M.p.: 155°-156° C.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:13])[C@H:5]([CH2:11]O)[NH:6][CH2:7][CH:8]([CH3:10])[CH3:9].COC(=O)[C@H](CO)N.O=S(Cl)[Cl:24].[CH3:26][C:27]1[CH:32]=[C:31]([N+:33]([O-:35])=[O:34])[CH:30]=[CH:29][C:28]=1[N:36]=[C:37]=[S:38]>>[ClH:24].[CH3:26][C:27]1[CH:32]=[C:31]([N+:33]([O-:35])=[O:34])[CH:30]=[CH:29][C:28]=1[N:36]=[C:37]1[N:6]([CH2:7][CH:8]([CH3:10])[CH3:9])[C@H:5]([C:4]([O:3][CH3:2])=[O:13])[CH2:11][S:38]1
Reactant: O=S(Cl)Cl
Reactant: Cc1cc([N+](=O)[O-])ccc1N=C=S
Reactant: COC(=O)[C@H](CO)NCC(C)C
Agent: COC(=O)[C@@H](N)CO
Agent: Cl
Product: COC(=O)[C@@H]1CSC(=Nc2ccc([N+](=O)[O-])cc2C)N1CC(C)C

Procedure:
(S)-N-isobutylserine methyl ester HCl salt was made from (L)-serine methyl ester as described in Method B3a. The ester was reacted with SOCl2, followed by 2-methyl-4-nitrophenyl isothiocyanate according to Method C2a to afford (4R)-2-(2-methyl-4-nitrophenylimino)-4-(methoxycarbonyl)-3-isobutyl-1,3-thiazolidine HCl salt.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:20][CH2:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C1(C)C=CC=CC=1>[Cl-:20].[C:14]1([P+:7]([CH2:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: O=C(CCl)OCc1ccccc1
Solvent: Cc1ccccc1
Product: O=C(C[P+](c1ccccc1)(c1ccccc1)c1ccccc1)OCc1ccccc1
Product: [Cl-]
Temperature: 25 °C
Yield: 90 %

Procedure:
23.6 g (0.1 mol) of triphenylphosphine were suspended in 70 ml of toluene. 18.5 g (0.1 mol) of benzyl chloroacetate were added dropwise and the mixture was heated at the boil for two hours. After cooling down to room temperature, the precipitated product was filtered off and washed with diethyl ether. Drying left 40.8 g (corresponding to a yield of 90%) of the title compound in the form of colorless crystals. The product was more than 99% pure.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[C:18]([C:19]([OH:21])=O)=[CH:17][N:16]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.[CH3:31][O:32][NH:33][CH3:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:31][O:32][N:33]([CH3:34])[C:19]([C:18]1[C:11]2[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)=[N:15][CH:14]=[N:13][C:12]=2[N:16]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:28])[CH3:29])[CH:17]=1)=[O:21]
Reactant: CNOC
Reactant: C[Si](C)(C)CCOCn1cc(C(=O)O)c2c(-c3cccc([N+](=O)[O-])c3)ncnc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CON(C)C(=O)c1cn(COCC[Si](C)(C)C)c2ncnc(-c3cccc([N+](=O)[O-])c3)c12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 4-(3-nitrophenyl)-7-[[2-(trimethylsilyl)ethoxy]methyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (637 mg, 1.54 mmol), methoxy(methyl)amine hydrochloride (298 mg, 3.06 mmol), was added N,N-dimethylformamide (20 mL), HATU (701 mg, 1.84 mmol) and DIPEA (793 mg, 6.14 mmol). The resulting solution was stirred for 2 hours at 25° C. and then quenched by the addition of water (50 mL). The reaction solution was extracted using ethyl acetate (×3), and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The product was purified by chromatography using silica gel, eluting with 50% ethyl acetate/petroleum ether. The product was collected and concentrated in vacuo to afford N-methoxy-N-methyl-4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide as a white solid. LRMS (ESI) calc'd for C21H28N5O5Si [M+H]+: 458, found 458. 1H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.59 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.18 (d, 8.4 Hz, 1H), 7.95 (s, 1H), 7.70 (t, J=7.8 Hz, 1H), 5.78 (s, 2H), 3.64 (t, J=8.2 Hz, 2H), 3.49 (s, 3H), 3.09 (s, 3H), 0.98 (t, J=8.2 Hz, 2H), 0.04 (s, 9H).
Reaction SMILES: [Te:1](=[O:5])(=[O:4])([OH:3])[OH:2].[Te:6](=[O:9])([OH:8])[OH:7].Cl.C([O-])([O-])=O.[Ca+2]>>[Te:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Te:6]([O-:9])([O-:8])=[O:7]
Reactant: O=[Te](=O)(O)O
Reactant: O=[Te](O)O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Product: O=[Te](=O)([O-])[O-]
Product: O=[Te]([O-])[O-]

Procedure:
Tellurate or tellurite glasses are prepared by starting with either telluric acid or tellurous acid, respectively. Weigh out 688.92 gm H2TeO4.2H2O or 532.83 gm of H2TeO3. Dissolve in 1000 ml. For H2TeO4, heating may be used to effect dissolution, but for H2TeO3, the solution must be kept cold, i.e. -- below 10° C. (About 50-75 ml of concentrated HCl may be added to aid dissolution of the H2TeO3). Weigh out 100.1 gm CaCO3 and dissolve into the acid solution to form a clear solution.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:45]2[NH:46][C:47]3[C:52]([C:53]=2[CH2:54][CH2:55][NH2:56])=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:40]=[CH:41][C:42]=1[O:43][CH3:44]>>[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:45]2[NH:46][C:47]3[C:52]([C:53]=2[CH2:54][CH2:55][NH:56][C:10](=[O:12])[CH2:9][CH2:8][C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:40]=[CH:41][C:42]=1[O:43][CH3:44]
Reactant: COc1ccc(-c2[nH]c3ccccc3c2CCN)cc1OC
Reactant: O=C(O)CCc1ccc(O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Product: COc1ccc(-c2[nH]c3ccccc3c2CCNC(=O)CCc2ccc(O)cc2)cc1OC
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 106.1 %

Procedure:
To a stirred solution of 3-(4-hydroxyphenyl)propionic acid (80 mg in 4 mL N,N-dimethylformamide) was added 1-hydroxybenzotriazole (78 mg) and the mixture cooled to 0° C. After 10 minutes, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (130 mg) was added. The mixture was warmed to room temperature and 2-[2-(3,4-dimethoxyphenyl)-1H-indol-3-yl]ethylamine (272 mg) was added. After 17 hours the reaction was quenched by the addition of water and extracted with ethyl acetate. The organic portion was washed with water, 0.5M sodium bisulfate and brine, dried over sodium sulfate and concentrated in vacuo. Purification by flash chromatography on silica gel (methylene chloride:methanol, 95:5) gave the title compound (227 mg). m/e=444 (M)
Reaction SMILES: CO[CH:3](OC)[C:4](=[N:7][OH:8])[C:5]#[N:6].[OH:11][CH2:12][CH2:13][NH:14][NH2:15].Cl.N>O.CO>[NH2:6][C:5]1[N:14]([CH2:13][CH2:12][OH:11])[N:15]=[CH:3][C:4]=1[N:7]=[O:8]
Reactant: NNCCO
Reactant: COC(OC)C(C#N)=NO
Agent: Cl
Agent: N
Solvent: O
Solvent: CO
Product: Nc1c(N=O)cnn1CCO
Temperature: 10 °C
Reaction time: 0.5 h
Yield: 72.6 %

Procedure:
To a flask having an inner volume of 50 ml and equipped with a stirring device, a thermometer and a reflux condenser were charged 4.59 g (30 mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of 94.3% by weight synthesized in the same manner as in Example 1, 2.98 g (31.5 mmol) of 2-hydroxyethylhydrazine with a purity of 80.5% by weight, 7.8 ml of methanol and 4.5 ml (54 mmol) of conc. hydrochloric acid, and the mixture was reacted at 50 to 52° C. for 3 hours. After completion of the reaction, 7 ml of water was added to the mixture and the resulting mixture was cooled up to 10° C. Then, 3.5 ml (58 mmol) of 28% by weight aqueous ammonia was gradually added dropwise to the mixture, and the mixture was stirred for 30 minutes while maintaining the liquid temperature to 5° C. or lower. The precipitated crystals were collected by filtration, and then, the crystals were washed with 2.5 ml of cold water and 2.5 ml of cold methanol, and dried under reduced pressure to obtain 3.40 g of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolation yield: 69.7%) as reddish orange crystals with a purity of 96.0% by weight (absolute calibration curve method by high performance liquid chromatography).
Reaction SMILES: [CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)=[C:7]([NH:23][C:24]([NH:26][C:27]2[C:32]([CH:33]([CH3:35])[CH3:34])=[CH:31][C:30]([NH:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)=[CH:29][C:28]=2[CH:44]([CH3:46])[CH3:45])=[O:25])[C:6]1=[O:47])[CH2:2][CH2:3][CH3:4].C=O.Cl.[C:51]([BH3-])#N.[Na+]>CO.O>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)=[C:7]([NH:23][C:24]([NH:26][C:27]2[C:32]([CH:33]([CH3:34])[CH3:35])=[CH:31][C:30]([N:36]([CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH3:51])=[CH:29][C:28]=2[CH:44]([CH3:46])[CH3:45])=[O:25])[C:6]1=[O:47])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cc(NCc3cccnc3)cc2C(C)C)c(-c2cccc(OC)c2)c2cccnc21
Reactant: [BH3-]C#N
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cc(N(C)Cc3cccnc3)cc2C(C)C)c(-c2cccc(OC)c2)c2cccnc21
Temperature: 25 °C
Reaction time: 5 h
Yield: 91 %

Procedure:
To a solution of N-[1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl]-N′-[2,6-diisopropyl-4-(3-pyridylmethylamino)-phenyl]urea (476 mg, 0.752 mmol) in methanol (5 ml) are added a 37% aqueous formaldehyde solution (122 mg, 1.50 ml) and conc. hydrochloric acid (0.13 ml, 1.50 ml) at room temperature. The mixture is cooled with ice, and the thereto is added sodium cyanoborohydride (71.0 mg, 1.13 ml), and the mixture is stirred at room temperature for 5 hours. To the mixture is added water, and the mixture is extracted with ethyl acetate. The organic layer is extracted twice with sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. The solvent is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to give the title compound (445 mg, 0.684 mmol) as colorless amorphous.
Reaction SMILES: [S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.C([Li])CCC.[B:15]([O:24][CH:25]([CH3:27])[CH3:26])([O:20][CH:21]([CH3:23])[CH3:22])OC(C)C.OC(C(O)(C)C)(C)C.Cl>O1CCCC1.C(OCC)C.O1CCOCC1>[CH3:27][C:25]1([CH3:26])[C:21]([CH3:22])([CH3:23])[O:20][B:15]([C:2]2[S:1][C:9]3[CH:8]=[CH:7][N:6]=[CH:5][C:4]=3[CH:3]=2)[O:24]1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: c1cc2sccc2cn1
Agent: CC(C)(O)C(C)(C)O
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: CC1(C)OB(c2cc3cnccc3s2)OC1(C)C
Temperature: -72.5 °C
Reaction time: 2 h
Yield: 82.7 %

Procedure:
To a −70° C. solution of thieno[3,2-c]pyridine (21.6 g) in 400 mL of dry tetrahydrofuran under nitrogen gas was added n-butyl lithium (99.9 ml of a 1.6 molar solution in hexanes) over about 15-20 minutes keeping the temperature below −65° C. The solution became cloudy and dark brown. After 45 minutes tri-isopropyl borate (33.06 g) was added and the mixture became homogeneous. The mixture was stirred at −70 to −75° C. for 2 hours. The mixture was allowed to warm to −30° C., then a solution of pinacol in 100 mL of diethyl ether was added over 4 minutes. The reaction mixture became an orange homogeneous solution. The temperature was allowed to warm to 5° C. and held at that temperature for 1 hour. The reaction mixture was neutralized (pH 7) very slowly with 40 mL of 4M hydrochloric acid in 1,4-dioxane, keeping the temperature below 10° C. A precipitate formed. The reaction mixture was stirred for 1 hour and then the solid was collected by filtration. The solid was dried under vacuum at 40° C. for 16 hours. The dry solid (36 g) was stirred with 400 mL of water for 1.5 hours. The slurry was filtered and the solid collected. The solid was dried under a flow of air for 60 hours to give the desired product (34.5 g). 1H NMR (400 MHz, Chloroform-d) δ ppm 1.21 (s, 12 H) 7.66-7.70 (m, 1 H) 7.80 (d, J=0.78 Hz, 1 H) 8.28 (d, J=5.65 Hz, 1 H) 8.98 (d, J=0.97 Hz, 1 H).