Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[B:11](OC(C)C)([O:16]C(C)C)[O:12]C(C)C.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[C:7]2[S:8][C:9]([B:11]([OH:16])[OH:12])=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Clc1cccc2ccsc12
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: OB(O)c1cc2cccc(Cl)c2s1
Temperature: -30 °C
Yield: 96.2 %

Procedure:
To a solution of 7-chlorobenzo[b]thiophene (1.0 g, 5.92 mmol) in THF (25 mL) at −78° C. was added nbutyllithium (7.41 mL, 11.8 mmol, 1.6 M solution). The reaction was allowed to warm to −30° C. then was cooled back to −78° C. and triisopropyl borate (2.23 g, 11.8 mmol) was added. The mixture was allowed to warm to 0° C., saturated ammonium chloride added and the organic phase separated off and concentrated in vacuo. To the residue was added aqueous sodium hydroxide (10 mL, 2N solution) followed by water (30 mL) and the mixture was washed with DCM. The aqueous phase was acidified with 2N sulfuric acid, and the resulting precipitate isolated by filtration and dried under vacuum to yield 7-chlorobenzo[b]thiophene-2-boronic acid (1.21 g, 96%) as white solid. 1H NMR (400 MHz, CDCl3) δ=7.41 (t, J=7.70 Hz, 1H), 7.50 (d, J=7.70 Hz, 1H), 7.91 (d, J=7.70 Hz, 1H), 8.03 (s, 1H), 8.63 (s, 2H); MS (ES+): m/z 211.86 [M+].
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH:9]([CH3:13])[CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1.[CH3:20]N(C)C(=O)C.IC.[H-].[Na+]>O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:20])[C:10](=[O:12])[CH:9]([CH3:13])[CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1
Reactant: CC1CN(C2CCCC2)c2nc(Cl)ncc2NC1=O
Reactant: CC(=O)N(C)C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CI
Product: CC1CN(C2CCCC2)c2nc(Cl)ncc2N(C)C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 0.056 g (0.0002 mole) of (rac)-2-chloro-9-cyclopentyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one, 0.5 mL of N,N-dimethylacetamide and 0.018 mL (0.0003 mole) of iodomethane was added 0.012 g (0.0003 mole) of 60% sodium hydride in oil at 0 degrees. The mixture was stirred at ambient temperature for 1 hour, then 10 mL of water was added. The precipitate collected by filtration to give 0.049 g of (rac)-2-chloro-9-cyclopentyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-1) as an yellow solid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH2:10])=[CH:5][CH:4]=1.[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K]>CN(C=O)C.O>[CH:9]([C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:15]2[C:11](=[O:21])[C:12]3[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:14]2=[O:16])=[CH:4][CH:5]=1)=[CH2:10]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: C=Cc1ccc(CCl)cc1
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: C=Cc1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Temperature: 70 °C
Yield: 46 %

Procedure:
To a stirred solution of 1-(chloromethyl)-4-vinylbenzene (10 g, 66 mmol) in DMF (100 mL) was added potassium phthalimide (13.3 g, 72.1 mmol), and the resultant reaction mixture was heated at 70° C. for 16 h. The reaction mixture was diluted with H2O and extracted with CHCl3. The combined CHCl3 layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Recrystallization from CH3OH afforded the title compound as an off-white solid (8 g, 46%): 1H NMR (400 MHz, CDCl3) δ 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H), 6.65 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.21 (d, J=10.8 Hz, 1H), 4.82 (s, 2H); GCMS m/z 263.2 ([M]+); IR (thin film) 3420, 1133, 718 cm−1.
Reaction SMILES: Cl.[CH:2]1([CH2:8][CH2:9][NH:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[C:16](=O)([O:22]C(C)(C)C)[O:17][C:18]([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:18]([O:17][C:16]([N:10]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:9][CH2:8][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1)=[O:22])([CH3:21])([CH3:20])[CH3:19]
Reactant: O=C(O)CCNCCC1CCCCC1
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Agent: Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N(CCC(=O)O)CCC1CCCCC1
Temperature: 25 °C
Yield: 62.8 %

Procedure:
Next, tetrahydrofuran (8 ml) was added to 3-[N-(2-cyclohexylethyl)amino]propionic acid hydrochloride (1.0 g, 4.2 mmol), and the mixture was stirred at room temperature. Di-t-butyl carbonate (1.1 g, 5.1 mmol) and triethylamine (1.3 ml, 9.3 mmol) were added to the mixture, the whole was stirred overnight, and then a 5% aqueous citric acid solution (10 ml) was added to the reaction mixture. The whole was extracted with chloroform (60 ml), and the obtained organic layer was washed with saturated brine (20 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-[N-(t-butoxycarbonyl)-N-(2-cyclohexylethyl)amino]propionic acid (0.79 g, 62%) as a colorless oily matter.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[N:16][C:17]=3[NH2:19])[NH:12][N:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C([O-])([O-])=O.[K+].[K+].CS(O[C@@H:31]1[CH2:35][CH2:34][O:33][CH2:32]1)(=O)=O>CN(C=O)C>[O:33]1[CH2:34][CH2:35][C@H:31]([N:12]2[C:13]3=[N:14][CH:15]=[N:16][C:17]([NH2:19])=[C:18]3[C:10]([C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=3)=[N:11]2)[CH2:32]1
Reactant: CS(=O)(=O)O[C@@H]1CCOC1
Reactant: Nc1ncnc2[nH]nc(-c3ccc([N+](=O)[O-])cc3)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1ncnc2c1c(-c1ccc([N+](=O)[O-])cc1)nn2[C@H]1CCOC1
Reaction time: 3 h

Procedure:
A solution of 3-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.5 g, 1.95 mmol), K2CO3 (1.08 g, 7.8 mmol), and (R)-tetrahydrofuran-3-yl methanesulfonate (0.389 g, 2.34 mmol) in DMF (20 mL) was brought to 80° C. under an argon atmosphere. The reaction mixture was left stirring for 3 hours, then cooled and filtered. The filtrate was concentrated in vacuo, but not to dryness. 20 mL of 0.1 sodium citrate was added causing a solid to form, which was collected by filtration to afford 1-((S)-tetrahydrofuran-3-yl)-3-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. ESI-MS m/z [M+H]+ found 327.6, calculated 327.3.
Reaction SMILES: [NH2:1][CH:2]([CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:3]([OH:5])=[O:4].C1COCC1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>[OH-].[Na+].O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([NH:1][CH:2]([CH2:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[C:3]([OH:5])=[O:4])(=[O:27])=[O:26])=[CH:21][CH:20]=1
Reactant: NC(CC1CCCCC1)C(=O)O
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C(CC1CCCCC1)NS(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
(RS)-phenylalanine (500.2 mg) was dissolved in H2O (50 ml) and 2N NaOH (1.5 ml). Rh/Al2O3 catalyst (500.5 mg) was added, and the whole was stirred overnight under a hydrogen atmosphere at atmospheric pressure. After the reaction was completed, Rh/Al2O3 was separated by filtration. The filtrate was concentrated to give crude (RS)-2-amino-3-cyclohexylpropanoic acid. Then, the crude (RS)-2-amino-3-cyclohexylpropanoic acid was dissolved in 2N NaOH (15.08 ml). THF (15 ml) and then 4-chlorobenzenesulfonyl chloride (3.196 g) were added, and the whole was stirred at room temperature overnight under argon. The reaction mixture was diluted with water, washed with ethyl acetate, acidified with 2N HCl and extracted 3 times with ethyl acetate. The combined ethyl acetate layers were washed with a saturated saline solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 80 g, ethyl acetate) and then by preparative TLC to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-3-cyclohexylpropanoic acid (200.9 mg).
Reaction SMILES: Cl.[CH3:2][O:3][NH2:4].N1C=CC=CC=1.[C:11]([C:14]1[CH:39]=[CH:38][C:17]([CH2:18][NH:19][C:20]2[C:30]3[CH2:29][CH2:28][N:27]([C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[CH2:26][CH2:25][C:24]=3[CH:23]=[CH:22][C:21]=2[Cl:37])=[CH:16][CH:15]=1)(=O)[CH3:12]>C(O)C>[Cl:37][C:21]1[CH:22]=[CH:23][C:24]2[CH2:25][CH2:26][N:27]([C:31](=[O:36])[C:32]([F:35])([F:33])[F:34])[CH2:28][CH2:29][C:30]=2[C:20]=1[NH:19][CH2:18][C:17]1[CH:16]=[CH:15][C:14]([C:11](=[N:4][O:3][CH3:2])[CH3:12])=[CH:39][CH:38]=1
Reactant: CON
Reactant: CC(=O)c1ccc(CNc2c(Cl)ccc3c2CCN(C(=O)C(F)(F)F)CC3)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: CON=C(C)c1ccc(CNc2c(Cl)ccc3c2CCN(C(=O)C(F)(F)F)CC3)cc1
Yield: 82.6 %

Procedure:
Add O-methylhydroxylamine hydrochloride (10 mg, 0.12 mmol) and pyridine (0.02 mL, 0.24 mmol) to a solution of 6-(4-acetyl-benzylamino)-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (50 mg, 0.12 mmol) in ethanol (10 mL). Heat the mixture to reflux for 1.5 h. Remove the solvent in vacuo and partition the residue between DCM and 0.1N aqueous HCl. Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (95:5 to 1:1 gradient over 30 min). Concentrate in vacuo to obtain 7-chloro-6-[4-(1-methoxyimino-ethyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (45 mg, 83%). MS (ES+) m/z: 454 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].N1C=CC=CC=1.[CH3:17][O:18][C:19](=[O:25])[CH2:20][S:21](Cl)(=[O:23])=[O:22].Cl>ClC(Cl)C>[CH3:17][O:18][C:19](=[O:25])[CH2:20][S:21](=[O:23])(=[O:22])[NH:4][C:3]1[C:2]([F:1])=[CH:8][C:7]([F:9])=[CH:6][C:5]=1[F:10]
Reactant: COC(=O)CS(=O)(=O)Cl
Reactant: Nc1c(F)cc(F)cc1F
Agent: Cl
Solvent: CC(Cl)Cl
Solvent: c1ccncc1
Product: COC(=O)CS(=O)(=O)Nc1c(F)cc(F)cc1F
Temperature: 0 °C
Reaction time: 12 h

Procedure:
0.76 g (5 mmol) of 2,4,6-trifluoroaniline is dissolved in 40 ml of dichloroethane with exclusion of moisture, 0.4 ml (5 mmol) of pyridine is added, 0.86 g (5 mmol) of chlorosulfonyl acetic acid methyl ester, dissolved in 10 ml of dichloroethane, is instilled at 0° C. and then it is stirred for 1 hour at 0° C. and 12 hours at room temperature. The reaction solution is then shaken out twice with 10 ml of 2N hydrochloric acid each, the phases are separated, the organic phase is dried on magnesium sulfate, filtered and evaporated to dryness. The residue is crystallized from diethyl ether/pentane 1:1. 790 mg (2.79 mmol)=55.79% of the theoretical yield is obtained as a crystallizate. Melting point 99-100° C.
Reaction SMILES: CS([O:5][CH:6]1[CH2:9][N:8]([C:10]([C:12]2[O:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][N:16]=2)=[O:11])[CH2:7]1)(=O)=O.[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1O)[CH:27]=[O:28]>>[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[O:5][CH:6]1[CH2:9][N:8]([C:10]([C:12]2[O:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][N:16]=2)=[O:11])[CH2:7]1)[CH:27]=[O:28]
Reactant: O=Cc1ccc(O)c(Cl)c1
Reactant: CS(=O)(=O)OC1CN(C(=O)c2nnc(-c3ccccc3)o2)C1
Product: O=Cc1ccc(OC2CN(C(=O)c3nnc(-c4ccccc4)o3)C2)c(Cl)c1
Yield: 34.5 %

Procedure:
Using a similar protocol as described in Example 9A but employing 1C (500 mg, 1.55 mmol) and 3-chloro-4-hydroxybenzaldehyde (250 mg, 1.60 mmol) as starting materials gave 205 mg (34%) of 10A as a solid. 1H NMR (500 MHz, CD3OD): δ 4.33 (m, 1H), 4.6-4.9 (m, 2H), 5.23 (m, 1H), 5.36 (m, 1H), 7.07 (d, 1H), 7.5-7.7 (m, 3H), 7.8-9.0 (m, 4H), 9.86 (s, 1H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][Br:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCCCCCCCCc1ccccc1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCCCCCCCc1ccccc1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
8-Phenyloctyl bromide was prepared from 8-phenyloctanol, carbon tetrabromide and triphenylphosphine in methylene chloride. A solution of 8-phenyloctanoic acid (19.8 mmol) in sieve dried tetrahydrofuran (5 ml) was reduced with diborane in tetrahydrofuran (30 ml, 29.1 mmol) at 20° C. for 4 hours to give 8-phenyloctanol. To an ice cold solution of the octanol (ca. 19.8 mmol) and carbon tetrabromide (21.98 mmol) in methylene chloride (50 ml) was added triphenylphosphine (22.30 mmol) in methylene chloride (50 ml) and the resulting solution was stirred for 2.5 hours. The volatiles were evaporated and the residue was taken up in ether (100 ml), cooled in ice, and filtered. The filtrate was evaporated and distilled to afford 8-phenyloctyl bromide as an oil. To 8-phenyloctyl bromide and 21.27 mmol of magnesium) in distilled tetrahydrofuran (40 ml) was added 2-(2-methoxyphenyl)-4,4-dimethyloxazoline (17.10 mmol) in tetrahydrofuran (20 ml). After stirring for 24 hours, the reaction mixture was similarly worked up to yield 2-[2-(8-phenyloctyl)phenyl]-4,4-dimethyloxazoline as an oil. A solution of the oxazoline (11.58 mmol) in methyl iodide (20 ml) as refluxed under argon for 18 hours. Removal of the volatiles afforded the corresponding 3,4,4-trimethyloxazolinium iodide as a white solid (mp 76.5°-78° D.). To an ice cold solution of the iodide (9.46 mmol) in methanol (35 ml) was added in portions sodium borohydride (9.20 mmol). Treatment of the reaction mixture as in Example 1(c) results in the isolation of the desired product as an oil.
Reaction SMILES: [F:1][B-](F)(F)F.N#[O+].C(OC([N:15]1[CH2:22][CH2:21][C@:20]2([CH3:26])[C:23]([CH3:25])([CH3:24])[C@H:16]1[CH2:17][C:18]1[C:30](N)=[CH:29][CH:28]=[CH:27][C:19]=12)=O)(C)(C)C>O1CCOCC1.CO>[F:1][C:30]1[C:18]2[CH2:17][C@@H:16]3[C:23]([CH3:25])([CH3:24])[C@:20]([CH3:26])([C:19]=2[CH:27]=[CH:28][CH:29]=1)[CH2:21][CH2:22][NH:15]3
Reactant: CC(C)(C)OC(=O)N1CC[C@@]2(C)c3cccc(N)c3C[C@@H]1C2(C)C
Reactant: F[B-](F)(F)F
Agent: N#[O+]
Solvent: CO
Solvent: C1COCCO1
Product: CC1(C)[C@H]2Cc3c(F)cccc3[C@]1(C)CCN2
Temperature: 50 °C
Reaction time: 8 h

Procedure:
A solution of nitrosonium tetrafluoroborate (0.25 g) in dioxane (2 mL) is added to a solution of (2R,6S)-10-amino-6,11,11-trimethyl-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester (0.10 g) in dioxane (2 mL). The solution is heated to 50° C. and stirred at this temperature overnight. The reaction solution is diluted with methanol and then concentrated under reduced pressure. The residue is purified by HPLC on reversed phase (MeCN/H2O/F3CCO2H) to yield the title product.
Reaction SMILES: NC1C=C(C(C2C=C3C(C(C=CC4C=CC=CC=4)=NN3COCC[Si](C)(C)C)=CC=2)=C)C=CC=1.[C:35]([NH:38][C:39]1[CH:40]=[C:41]([C:45]([C:47]2[CH:55]=[C:54]3[C:50]([C:51]([CH:64]=[CH:65][C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)=[N:52][N:53]3COCC[Si](C)(C)C)=[CH:49][CH:48]=2)=[CH2:46])[CH:42]=[CH:43][CH:44]=1)(=[O:37])[CH3:36]>C(OCC)(=O)C.CCCCCC>[C:35]([NH:38][C:39]1[CH:40]=[C:41]([C:45]([C:47]2[CH:55]=[C:54]3[C:50]([C:51]([CH:64]=[CH:65][C:66]4[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=4)=[N:52][NH:53]3)=[CH:49][CH:48]=2)=[CH2:46])[CH:42]=[CH:43][CH:44]=1)(=[O:37])[CH3:36]
Reactant: C=C(c1cccc(NC(C)=O)c1)c1ccc2c(C=Cc3ccccc3)nn(COCC[Si](C)(C)C)c2c1
Agent: C=C(c1cccc(N)c1)c1ccc2c(C=Cc3ccccc3)nn(COCC[Si](C)(C)C)c2c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: C=C(c1cccc(NC(C)=O)c1)c1ccc2c(C=Cc3ccccc3)n[nH]c2c1

Procedure:
6-(1-(3-Aminophenyl)-vinyl)-3-styryl-1-[2-trimethylsilanyl-ethoxymethyl]-1H-indazole was converted to 6-(1-(3-acetamido-phenyl)-vinyl)-3-styryl-1-[2-trimethylsilanyl-ethoxymethyl]-1H-indazole as described for Example 12(a): Rfsm 0.42, p 0.26 (ethyl acetate-hexane 4:6); FTIR (thin film) 3305, 3059, 2952, 1667, 1608, 1585, 1555, 1486, 1448, 1433, 1369, 1306, 1249, 1076, 912, 859, 836, 748, 693 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, 1H, J=8.5 Hz), 7.7-7.4 (m, 9H), 7.35 (m, 2H), 7.26 (dd, 1H, J=1.3, 8.4 Hz), 7.16 (bd, 1H, J=7.8 Hz), 5.75 (s, 2H), 5.62 (s, 1H), 5.61 (s, 1H), 3.66 (t, 2H, J=8.2 Hz), 2.16 (s, 3H), 0.98 (t, 2H, J=8.2 Hz), −0.02 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 169.8, 150.9, 144.6, 143.5, 142.8, 142.0, 139.4, 138.6, 132.9, 130.3, 129.3, 127.9, 125.6, 124.2, 123.7, 122.0, 121.3, 121.0, 117.1, 110.8, 68.0, 25.8, 19.1, 0.0; HRMS (FAB) [M+Na]/z Calc'd 532.2396, found 532.2410.
Reaction SMILES: [C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].N1CC[CH:16]([N:19]2[CH2:25][CH2:24][C:23]3[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=3[NH:21][C:20]2=[O:30])[CH2:15]C1.C(OC)(C)(C)C>CN(C)C=O>[N:8]1([C:1]([N:3]2[CH2:4][CH2:15][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:6][CH2:7]2)=[O:2])[CH:12]=[CH:11][N:10]=[CH:9]1
Reactant: O=C1Nc2ccccc2CCN1C1CCNCC1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: COC(C)(C)C
Solvent: CN(C)C=O
Product: O=C1Nc2ccccc2CCN1C1CCN(C(=O)n2ccnc2)CC1
Temperature: 25 °C

Procedure:
10 g (44.8 mmol) of carbonyldiimidazole (I) are in 40 mL dimethylformamide at 40 to 50° C. dissolved. Then 10.0 g (40.8 mmol) of 1,3,4,5-tetrahydro-3-(4-piperidinyl)-2H-1,3-benzodiazepin-2-one (H) are added batchwise. The suspension formed is liquefied by the addition of 40 mL tert.butyl-methylether and cooled to ambient temperature. After the addition of another 40 mL tert.butyl-methylether the suspension is filtered, the isolated solid is washed with 100 mL tert.butyl-methylether and dried.
Reaction SMILES: Cl.[CH3:2][Si:3]([CH3:20])([CH3:19])[CH2:4][CH2:5][O:6][CH2:7][N:8]1[C:12]2=[N:13][CH:14]=[C:15]([NH:17][NH2:18])[N:16]=[C:11]2[CH:10]=[CH:9]1.[CH3:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[C:28](O)=[O:29].C(N(CC)CC)C.CCN=C=NCCCN(C)C>ClCCl>[CH3:2][Si:3]([CH3:20])([CH3:19])[CH2:4][CH2:5][O:6][CH2:7][N:8]1[C:12]2=[N:13][CH:14]=[C:15]([NH:17][NH:18][C:28]([CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH:22]3[CH3:21])=[O:29])[N:16]=[C:11]2[CH:10]=[CH:9]1
Reactant: CC1CCCCC1C(=O)O
Reactant: C[Si](C)(C)CCOCn1ccc2nc(NN)cnc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1CCCCC1C(=O)NNc1cnc2c(ccn2COCC[Si](C)(C)C)n1
Temperature: 0 °C
Reaction time: 3 h
Yield: 35.5 %

Procedure:
A flask containing a mixture of [5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-hydrazine hydrochloride (336 mg, 1.06 mmol) and (+/−)-2-methyl-1-cyclohexane-carboxylic acid (0.18 mL, 1.22 mmol) in dry dichloromethane (11 mL) was cooled to 0° C. (ice bath) under nitrogen atmosphere. To this cooled mixture was added triethylamine (0.31 mL, 2.1 mmol) and EDCI (278 mg, 1.45 mmol). After 30 minutes the cooling bath was removed and the material was stirred for 3 hours. An aqueous solution of 5% sodium bicarbonate (40 mL) and methylene chloride (30 mL) were added and the mixture was shaken in a reparatory funnel. The organic phase was collected and washed with brine (40 mL). The aqueous phases were back extracted with methylene chloride (2×30 mL). The organic phases were combined, dried (MgSO4), filtered and stripped. The crude remainder was purified by preparative TLC, using 45% ethyl acetate in hexanes to elute. The product band was collected, affording 152 mg of (+/−)-2-methyl-cyclohexanecarboxylic acid-N′-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-hydrazide as a golden brown oil, which solidified on standing. MS (M+H)+=404.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH:4](Cl)[CH2:5][S:6][CH2:7][C:8]([OH:10])=[O:9].[N-:13]=[N+:14]=[N-:15].[Na+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].O>[CH3:1][O:2][C:3](=[O:12])[CH:4]([N:13]=[N+:14]=[N-:15])[CH2:5][S:6][CH2:7][C:8]([OH:10])=[O:9]
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)C(Cl)CSCC(=O)O
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: COC(=O)C(CSCC(=O)O)N=[N+]=[N-]
Yield: 88.3 %

Procedure:
1.00 gram (4.70 mmoles) of the 2-chloro-3-carboxymethylmercapto-propionic acid methyl ester produced in Example 9 was stirred with 0.46 gram (7.08 mmoles) of sodium azide and 0.10 gram of Aliquat 336 in 2 ml of water for 15 hours at 50° C. After working up according to Example 2 there were obtained 0.91 gram (88% of theory) of 2-azido-3-carboxymethylmercapto-propionic acid methyl ester as an analytically pure material.
Reaction SMILES: [CH:1](=O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([BH3-])#N.[Na+]>C(O)(=O)C.CO>[CH2:11]([NH:18][CH2:1]/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: NCc1ccccc1
Reactant: O=CC=Cc1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: C(=C/c1ccccc1)\CNCc1ccccc1
Reaction time: 18 h

Procedure:
Cinnamaldehyde and benzylamine were dissolved in 1% acetic acid in methanol under an atmosphere of dry nitrogen. Sodium cyanoborohydride (~1 equivalent) was added, and stirring was continued for 18 hours at which time the solvent was removed under reduced pressure. The residue was suspended in ether, washed with 5% NaHCO3 and brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:8]([O:10]CC)=[O:9])=[C:5]([CH3:7])[N:6]=1.[OH-].[Na+]>O1CCCC1.O>[NH2:1][C:2]1[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=1
Reactant: CCOC(=O)c1sc(N)nc1C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1nc(N)sc1C(=O)O
Yield: 92.6 %

Procedure:
A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was neutralized with 5% hydrochloric acid solution to pH 5˜6. The precipitate obtained was collected by filtration and dried to afford the crude 2-amino-4-methylthiazole-5-carboxylic acid (5.20 g, 94%): 1H NMR (300 MHz, DMSO-d6) δ 7.63 (s, 2H), 2.30 (s, 3H); MS (ES+) m/z 159.1 (M+1).
Reaction SMILES: Cl[C:2]1[O:3][C:4]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=3)[CH:10]=[CH:9][CH:8]=2)=[CH:5][N:6]=1.C([O-])([O-])=O.[K+].[K+].[CH:27]1([SH:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.O>CC(O)C>[CH:27]1([S:33][C:2]2[O:3][C:4]([C:7]3[N:12]=[C:11]([NH:13][C:14]4[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=4)[CH:10]=[CH:9][CH:8]=3)=[CH:5][N:6]=2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: Cc1ccnc(Nc2cccc(-c3cnc(Cl)o3)n2)c1
Reactant: SC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: O
Product: Cc1ccnc(Nc2cccc(-c3cnc(SC4CCCCC4)o3)n2)c1
Yield: 70.6 %

Procedure:
A mixture of [6-(2-chloro-oxazol-5-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine (50 mg, 0.174 mmol), K2CO3 (72 mg, 0.523 mmol) and cyclohexanethiol (64 μl, 0.523 mmol) in iPrOH (5 ml) were heated to reflux for 18 h. The cooled mixture was treated with water and extracted with DCM. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure to a yellow gum. The gum was taken up in a minimum of DCM and precipitated with n-pentane to afford the title compound as a beige solid (45 mg, 71%). 1H NMR (300 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.10 (s, 1H), 7.56-7.78 (m, 4H), 7.17 (d, J=5.9 Hz, 1H), 6.75 (s, 1H), 3.71 (m, 1H), 2.31 (s, 3H), 2.08 (m, 2H), 1.64 (m, 8H). (ESI+) m/z 367 (M+H)+.