Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.O>[Cl:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(Br)cc1
Reactant: OB(O)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(-c2cccc(Cl)c2)cc1
Temperature: 0 °C
Yield: 90.9 %

Procedure:
A solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate H, 3 g, 9.6 mmol), 3-chlorophenylboronic acid (1.8 g, 11.5 mmol) and K2CO3 (3.9 g, 28.8 mmol) in acetonitrile:water (4:1) was degassed for 20 min. Tetrakis triphenylphosphine palladium (300 mg) was added and heated at reflux for 18 h. After completion, the reaction mixture was poured into ice water (100 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2SO4 filtered and evaporated. The crude residue was purified by column chromatography (SiO2) using EtOAc: Pet ether to give (3 g, 91%) tert-butyl (trans)-2-(3′-chlorobiphenyl-4-yl)cyclopropylcarbamate as a white solid.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH3:2].[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:29]2[C:34]([CH3:35])=[CH:33][C:32]([O:36][CH2:37][C:38](OC)=[O:39])=[CH:31][C:30]=2[CH3:42])=[C:10]2[C:14]=1[C@H:13]([O:15][C:16]1[CH:28]=[CH:27][C:19]3[C@H:20]([CH2:23][C:24]([OH:26])=[O:25])[CH2:21][O:22][C:18]=3[CH:17]=1)[CH2:12][CH2:11]2>O1CCCC1.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:29]2[C:34]([CH3:35])=[CH:33][C:32]([O:36][CH2:37][C:38]3([OH:39])[CH2:2][CH2:1]3)=[CH:31][C:30]=2[CH3:42])=[C:10]2[C:14]=1[C@H:13]([O:15][C:16]1[CH:28]=[CH:27][C:19]3[C@H:20]([CH2:23][C:24]([OH:26])=[O:25])[CH2:21][O:22][C:18]=3[CH:17]=1)[CH2:12][CH2:11]2
Reactant: COC(=O)COc1cc(C)c(-c2ccc(F)c3c2CC[C@H]3Oc2ccc3c(c2)OC[C@H]3CC(=O)O)c(C)c1
Reactant: CC[Mg]Cl
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Solvent: C1CCOC1
Product: Cc1cc(OCC2(O)CC2)cc(C)c1-c1ccc(F)c2c1CC[C@H]2Oc1ccc2c(c1)OC[C@H]2CC(=O)O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Ethylmagnesium chloride (380 μL of a 1 M solution in tetrahydrofurane) is added dropwise under argon to a solution of 2-((S)-6-((R)-7-fluoro-4-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid in tetrahydrofurane (4 mL). The mixture is stirred at room temperature for 30 minutes. Ti(OiPr)4 (120 μL) is added dropwise and after stirring for 30 minutes ethylmagnesium chloride (1.15 mL of a 1 M solution in tetrahydrofurane) is added dropwise. The mixture is stirred for 2 hours, partitioned between ethylacetate and saturated aqueous NH4Cl solution and stirred vigorously for 30 minutes. After filtering over celite the phases are separated, the aqueous phase is extracted with diethylether and the combined organic phases are washed with brine and dried (MgSO4). The solvents are evaporated and the residue is purified by HPLC on reversed phase. Yield: 38 mg; LC (method 8): tR=0.38 min; Mass spectrum (ESI+): m/z=519 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:10])[CH:6]=[CH:7][C:8]=1[Br:9].[H-].[Na+].Br[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[Br:9])[O:10][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)CBr
Reactant: COc1cc(O)ccc1Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(Br)c(OC)c1
Temperature: 25 °C
Yield: 75.6 %

Procedure:
3-Methoxy-4-bromophenol D8 (6.95 g, 34 mmoles) in dry dimethylformamide (100 ml) at 0° C. was treated with sodium hydride (80% dispersion in oil) (1.13 g, 37 mmoles). After 30 mins ethyl bromoacetate (3.8 ml, 34 mmoles) was added and the mixture allowed to warm to room temperature over 1 hr. The mixture was concentrated in vacuo and the residue partitioned between water and diethyl ether. The organic layer was washed several times with water and then dried (Na2SO4) and evaporated to dryness. Flash chromatography on TLC silica gel eluting with dichloromethane gave the title compound (D9) (7.43 g, 75%)
Reaction SMILES: [F:1][CH:2]([F:34])[N:3]1[CH:7]=[C:6]([S:8]([N:11]2[C:15]([C:16]3[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=3)=[C:14]([F:23])[C:13]([CH2:24][N:25](C)[C:26](=O)OC(C)(C)C)=[CH:12]2)(=[O:10])=[O:9])[CH:5]=[N:4]1.C(OCC)(=O)C.[ClH:41]>C(O)C>[ClH:41].[F:34][CH:2]([F:1])[N:3]1[CH:7]=[C:6]([S:8]([N:11]2[C:15]([C:16]3[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=3)=[C:14]([F:23])[C:13]([CH2:24][NH:25][CH3:26])=[CH:12]2)(=[O:9])=[O:10])[CH:5]=[N:4]1
Reactant: CN(Cc1cn(S(=O)(=O)c2cnn(C(F)F)c2)c(-c2cccnc2F)c1F)C(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCO
Product: CNCc1cn(S(=O)(=O)c2cnn(C(F)F)c2)c(-c2cccnc2F)c1F
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 72 %

Procedure:
tert-Butyl {[1-{[1-(difluoromethyl)-1H-pyrazol-4-yl]sulfonyl}-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate (380 mg) was dissolved in ethanol (10 mL), 4 mol/L hydrogen chloride-ethyl acetate solution (10 mL) was added, and the mixture was stirred at 40° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized from ethyl acetate to give the title compound as colorless crystals (yield 240 mg, 72%).
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1)=[O:5].C(N(CC)CC)C.[CH:27]1[C:37]2[N:36]3[CH:38]=[CH:39][CH:40]=[C:35]3[CH2:34][CH2:33][NH:32][C:31]=2[CH:30]=[CH:29][CH:28]=1>C(Cl)Cl.C(OCC)(=O)C>[CH:27]1[C:37]2[N:36]3[CH:38]=[CH:39][CH:40]=[C:35]3[CH2:34][CH2:33][N:32]([C:11]([C:10]3[CH:14]=[CH:15][C:7]([NH:6][C:4](=[O:5])[C:3]4[CH:16]=[CH:17][CH:18]=[CH:19][C:2]=4[CH3:1])=[CH:8][CH:9]=3)=[O:12])[C:31]=2[CH:30]=[CH:29][CH:28]=1
Reactant: c1ccc2c(c1)NCCc1cccn1-2
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCc3cccn3-c3ccccc32)cc1
Temperature: 0 °C
Reaction time: 48 h

Procedure:
To a mixture of 1.37 g (5 mmol) of 4-[(2-methylbenzoyl)amino]benzoyl chloride in 10 ml of methylene chloride, cooled to 0° C. is added 7 mmol of triethylamine and 5 mmol of 6,7-dihydro-5H-pyrrolo-[1,2-a][1,5]benzodiazepine. The cooling bath is removed and the reaction mixture is allowed to stir at room temperature for 48 hours. The volatiles are removed in vacuo to give a residue. The residue is dissolved in 100 ml of ethyl acetate and washed with water, 2N citric acid, aqueous NaHCO3 and brine. The solution is dried with Na2SO4 and the solvent removed in vacuo to give a solid. The solid is triturated with ether-hexane to give the desired product, mass spectrum (CI):422(M+H).
Reaction SMILES: [NH2:1][S:2]([C:5]1[CH:6]=[C:7]([C:11](=[N:13][OH:14])[NH2:12])[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].C(C1C=C(S(N)(=O)=O)C=CC=1)#N.[CH3:27][O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36](O)=O)[CH:33]=[CH:32][C:31]=1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH3:45]>>[CH3:27][O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36]2[O:14][N:13]=[C:11]([C:7]3[CH:6]=[C:5]([S:2]([NH2:1])(=[O:4])=[O:3])[CH:10]=[CH:9][CH:8]=3)[N:12]=2)[CH:33]=[CH:32][C:31]=1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH3:45]
Reactant: COCc1cc(C(=O)O)ccc1-c1ccccc1C
Reactant: NC(=NO)c1cccc(S(N)(=O)=O)c1
Agent: N#Cc1cccc(S(N)(=O)=O)c1
Product: COCc1cc(-c2nc(-c3cccc(S(N)(=O)=O)c3)no2)ccc1-c1ccccc1C

Procedure:
The title compound was obtained following procedure and work up described for example 107, step 1, but starting from 3-(aminosulfonyl)-N′-hydroxybenzenecarboximidamide, prepared as described in WO 2006/013104 A1 from 3-cyanobenzene-1-sulfonamide (Maybridge; GK 03054), (1.50 g; 6.97 mmol) and Intermediate 28 (1.79 g; 6.97 mmol), followed by a recrystallization from DCM gave the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.58-8.57 (m, 1H), 8.35-8.32 (m, 2H), 8.20-8.17 (m, 1H), 8.08-8.05 (m, 1H), 7.83 (t, J=7.8 Hz, 1H), 7.59 (bs, 2H), 7.43 (d, J=8 Hz, 1H), 7.36-7.27 (m, 3H), 7.16-7.13 (m, 1H), 4.23 (d, J=12.6 Hz, 1H), 4.16 (d, J=12.6 Hz, 1H), 3.25 (s, 3H), 2.03 (s, 3H). LC/MS (Method B): 436.3 (M+H)+. HPLC (Method A) Rt 5.37 min (purity: 99.6%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[CH:13]=[C:12](Cl)[N:11]=[C:10]([F:22])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[C:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)#[N:24].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>>[NH2:20][C:17]1[O:18][CH2:19][C@:15]2([C:14]3[CH:13]=[C:12]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[N:11]=[C:10]([F:22])[C:9]=3[O:8][C:5]3[C:4]2=[CH:3][C:2]([C:29]2[CH:30]=[C:25]([CH:26]=[CH:27][CH:28]=2)[C:23]#[N:24])=[CH:7][CH:6]=3)[N:16]=1
Reactant: C1COCCN1
Reactant: N#Cc1cccc(B(O)O)c1
Reactant: NC1=N[C@@]2(CO1)c1cc(Br)ccc1Oc1c2cc(Cl)nc1F
Product: N#Cc1cccc(-c2ccc3c(c2)[C@@]2(COC(N)=N2)c2cc(N4CCOCC4)nc(F)c2O3)c1

Procedure:
The titled compound was synthesized by steps analogous to those described in Method CC4 above using (S)-7-bromo-3-chloro-1-fluoro-5′H-spiro[chromeno[2,3-c]pyridine-5,4′ oxazol]-2′-amine (prepared as described in Method BB33), 3-cyanophenylboronic acid and morpholine.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([F:22])[CH:16]=2)[S:6]1(=[O:24])=[O:23].[CH3:25][NH2:26].Cl>>[ClH:1].[F:22][C:17]1[CH:16]=[C:15]([N:7]2[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[CH2:10][N:5]([CH2:4][CH2:3][CH2:2][NH:26][CH3:25])[S:6]2(=[O:24])=[O:23])[CH:20]=[CH:19][C:18]=1[F:21]
Reactant: CN
Reactant: O=S1(=O)N(CCCCl)Cc2ccccc2N1c1ccc(F)c(F)c1
Agent: Cl
Product: CNCCCN1Cc2ccccc2N(c2ccc(F)c(F)c2)S1(=O)=O

Procedure:
In an analogous manner to Example 1, step 8, 3-(3-chloropropyl)-1-(3,4-difluorophenyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide (71 mg) was reacted with methylamine and then treated with HCl to provide 3-[1-(3,4-difluorophenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzothiadiazin-3-yl]-N-methyl propan-1-amine hydrochloride (53 mg):
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[Br:7][C:8]1[N:13]=[C:12]([NH2:14])[CH:11]=[CH:10][CH:9]=1>>[Br:7][C:8]1[N:13]=[C:12]([NH:14][C:3](=[O:4])[CH:2]([CH3:6])[CH3:1])[CH:11]=[CH:10][CH:9]=1
Reactant: CC(C)C(=O)Cl
Reactant: Nc1cccc(Br)n1
Product: CC(C)C(=O)Nc1cccc(Br)n1

Procedure:
Prepared by Procedure Q1 using 2-methylpropanoyl chloride and 6-bromo-2-pyridinamine: ESMS m/e: 242.8 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=1)[NH:14][CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[C:40]1([S:50](Cl)(=[O:52])=[O:51])[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][CH:41]=1>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=1)[N:14]([S:50]([C:40]1[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=[CH:42][CH:41]=1)(=[O:52])=[O:51])[CH2:13][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2ccc3c(c2)CCNC3c2ccc(OCCN3CCCC3)cc2)cc1
Reactant: O=S(=O)(Cl)c1cccc2ccccc12
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=S(=O)(c1cccc2ccccc12)N1CCc2cc(OCc3ccccc3)ccc2C1c1ccc(OCCN2CCCC2)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of 6-benzyloxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-1,2,3,4-tetrahydroisoquinoline (0.015 g, 0.04 mmol) and Et3N (0.01 ml, 0.07 mmol) in anhydrous THF (0.35 ml) was added to a solution of 1-naphthalenesulfonyl chloride (0.04 mmol) in anhydrous THF (0.4 ml) at rt in a sealed reaction vessel. The resulting suspension was stirred at rt for 20 hr, then evaporated to dryness. The product was suspended in a mixture of H2O(0.4 ml) and saturated NaHCO3 solution (0.4 ml), then extracted with CH2Cl2 (3×0.75 ml). The combined extracts were evaporated to dryness to give the crude product. Purification by reverse-phase HPLC on a Primesphere C-18HC (50.0 mm×10.0 mm column with 5 m particle size) column, eluting with a linear gradient starting at time 0 min. of H2O:CH3CN 1% TFA/H2O (85:10:5), increasing to H2O:CH3CN:1% TFA/H2O (5:90:5) at 8 min., detected on a Micromass Platform 2 mass spectrometer (DAD 190-600 nM) gave material which, after evaporation to dryness, was purified by reverse-phase HPLC on a Primesphere C-18HC (3.0 mm×2.0 mm column with 5 m particle size) column, eluting with a linear gradient starting at time 0 min. of H2O:CH3CN:TFA (99.9:0:0.1), increasing to H2O:CH3CN:TFA (0:99.9:0.1) at 4 min., detected with a UV detector (300 nM +/−90 nM and 254 nM +/−25 nM), gave an eluent that was evaporated to dryness to give the named product. MS m/e 583 (M++1).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([Cl:25])=[C:7]([C:21]([Cl:24])=[CH:22][CH:23]=1)[CH2:8][O:9][C:10]1[C:11]2[N:12]([C:16]([Br:20])=[C:17]([CH3:19])[N:18]=2)[CH:13]=[CH:14][CH:15]=1)(=[O:3])[CH3:2].[H-].[Na+].I[CH3:29].O>CN(C)C=O>[Br:20][C:16]1[N:12]2[CH:13]=[CH:14][CH:15]=[C:10]([O:9][CH2:8][C:7]3[C:21]([Cl:24])=[CH:22][CH:23]=[C:5]([N:4]([C:1](=[O:3])[CH3:2])[CH3:29])[C:6]=3[Cl:25])[C:11]2=[N:18][C:17]=1[CH3:19]
Reactant: CC(=O)Nc1ccc(Cl)c(COc2cccn3c(Br)c(C)nc23)c1Cl
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)N(C)c1ccc(Cl)c(COc2cccn3c(Br)c(C)nc23)c1Cl
Yield: 58.9 %

Procedure:
To a solution of 8-(3-acetylamino-2,6-dichlorobenzyloxy)-3-bromo-2-methylimidazo[1,2-a]pyridine (222 mg) in N,N-dimethylformamide (2 ml) was added sodium hydride (24 mg, 60% oil dispersion) in one portion at ambient temperature. The mixture was stirred for half an hour at the same temperature and iodomethane (142 mg) was added thereto. After stirring for half an hour, the mixture was poured into water. The separated oil was extracted with ethyl acetate. The extracts were washed with water, dried, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel to give 3-bromo-8-[2,6-dichloro-3-(N-acetyl-N-methylamino)benzyloxy]-2-methylimidazo[1,2-a]pyridine (135 mg) as a solid.
Reaction SMILES: [ClH:1].Cl.[NH:3]1[CH2:7][CH2:6][CH2:5][C@H:4]1[C:8]1[O:16][C:11]2=[CH:12][N:13]=[CH:14][CH:15]=[C:10]2[CH:9]=1.[C:17]([O-])([O-])=O.[K+].[K+]>C(O)=O.C=O>[ClH:1].[ClH:1].[CH3:17][N:3]1[CH2:7][CH2:6][CH2:5][C@H:4]1[C:8]1[O:16][C:11]2=[CH:12][N:13]=[CH:14][CH:15]=[C:10]2[CH:9]=1
Reactant: c1cc2cc([C@@H]3CCCN3)oc2cn1
Reactant: O=C([O-])[O-]
Agent: C=O
Agent: Cl
Agent: [K+]
Solvent: O=CO
Product: CN1CCC[C@H]1c1cc2ccncc2o1
Temperature: 25 °C

Procedure:
A 120 mg sample of the compound from Example 9 above was dissolved in 4 mL of formic acid and 2 mL of formalin, and the reaction mixture was heated at reflux for 30 minutes. The reaction mixture was cooled to ambient temperature and poured into saturated K2CO3 solution. The resulting mixture was extracted with CH2Cl2, the extract was dried, and the solvent was removed. The residue was chromatographed on silica gel, and the compound was converted to the salt by treatment with HCl/ether: 1H NMR (D2O, 300 MHz) δ 2.30-2.40 (m, 3H), 2.50-2.74 (m, 1H), 2.98 (s, 3H), 3.45 (br d, 1H), 3.85 (br s, 1H), 4.97 (t, 1H), 7.47 (s, 1H), 8.08 (d, 1H), 8.51 (d, 1H), 9.10 (s, 1H); MS m/z: 203 (M+H)+ ; Anal. Calcd for C12H14N2O·2 HCl.0.5H2O: C, 50.70; H, 6.03; N, 9.86. Found: C, 50.69; H, 6.09; N, 9.61.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.[C:9]1([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][C:16]2=O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([BH3-])#N.[Na+]>CO>[CH:1]1([NH:4][C@@H:16]2[CH2:17][CH2:18][CH2:19][CH2:20][C@@H:15]2[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:3][CH2:2]1.[CH:1]1([NH:4][C@@H:16]2[CH2:17][CH2:18][CH2:19][CH2:20][C@H:15]2[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:3][CH2:2]1
Reactant: NC1CC1
Reactant: O=C1CCCCC1c1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: c1ccc([C@@H]2CCCC[C@H]2NC2CC2)cc1
Product: c1ccc([C@H]2CCCC[C@H]2NC2CC2)cc1
Temperature: 0 °C
Reaction time: 3.5 h
Yield: 23 %
Yield: 44 %

Procedure:
To a cooled solution of 2.78 ml (40 mmol) of cyclopropylamine and 2.87 ml (50 mmol) of acetic acid, together with 5 g of 3 Å molecular sieves, in 50 ml of methanol, are added 3.5 g (20 mmol) of 2-phenylcyclohexanone. The reaction mixture is stirred for 3.5 hrs at reflux. The reaction mixture is then cooled to 0° C. and 3 g (50 mmol) of sodium cyanoborohydride are slowly added and the reaction mixture is further stirred for 2 hrs at reflux. The cooled reaction mixture is then filtered over a cake of diatomaceous earth. The cake is washed twice by 80 ml of methanol and the combined methanolic extracts are concentrated under vacuum. 100 ml of water are then added to the residue and the pH is ajusted to 12 with a 1 N solution of sodium hydroxyde. The watery layer is extracted with 100 ml of ethyl acetate. The organic layer is washed twice by brine and dried over magnesium sulfate to yield after concentration 3.52 g of a yellow oil. Column chromatography on silica gel (gradient heptane/ethyl acetate) yields 1.0 g (23% yield) of cis-N-cyclopropyl-2-phenylcyclo-hexanamine as a yellow oil (M+H=216) and 1.9 g (44% yield) of trans-N-cyclopropyl-2-phenylcyclohexanamine as a colorless oil (M+H=216).
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][S:10][CH:9]1[C:13]([OH:15])=O)=O)(C)(C)C.C1C=CC(/[C:22](/[C:25]2[CH:30]=[CH:29][C:28]([N+]([O-])=O)=[CH:27][CH:26]=2)=[N:23]/O)=CC=1.[C:34]([C:38]1[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=1)([CH3:37])([CH3:36])[CH3:35].C(N)C1C=CC=CC=1>>[CH2:22]([NH:23][C:13]([CH:9]1[N:8]([S:44]([C:41]2[CH:42]=[CH:43][C:38]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:39][CH:40]=2)(=[O:46])=[O:45])[CH2:12][CH2:11][S:10]1)=[O:15])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)(C)OC(=O)N1CCSC1C(=O)O
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: O=[N+]([O-])c1ccc(/C(=N\O)c2ccccc2)cc1
Solvent: NCc1ccccc1
Product: CC(C)(C)c1ccc(S(=O)(=O)N2CCSC2C(=O)NCc2ccccc2)cc1

Procedure:
Following the general solid phase method as outlined Example 33, starting from 3-(tert-butoxycarbonyl)-1,3-thiazolidine-2-carboxylic acid, Kaiser oxime resin, 4-tert-butylbenzenesulfonyl chloride and benzylamine, the title compound was obtained in 97.1% purity by HPLC.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.C(C#N)(=O)[C:9]([CH3:12])([CH3:11])[CH3:10].S(=O)(=O)(O)O.[NH2:21][NH:22][C:23]([NH:25][NH2:26])=[S:24]>Cl>[NH2:26][N:25]1[C:5](=[O:7])[C:6]([C:9]([CH3:10])([CH3:11])[CH3:12])=[N:21][N:22]=[C:23]1[SH:24]
Reactant: NNC(=S)NN
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)C(=O)C#N
Agent: Cl
Agent: O=S(=O)(O)O
Product: CC(C)(C)c1nnc(S)n(N)c1=O
Reaction time: 2 h
Yield: 95.9 %

Procedure:
First 5.12 kg (50 mols) of acetic anhydride and then 2.78 kg (25 mols) of pivaloyl cyanide were introduced, in each case at room temperature, into 9.81 kg (100 mols) of concentrated sulphuric acid which had been initially introduced into the reaction vessel. After subsequently stirring this reaction mixture for 2 hours, it was stirred into a solution of 2.66 kg (25 mols) of thiocarbohydrazide in 30 liters of 1 N HCl at 20°-30° C. When the addition had ended, the mixture was subsequently stirred for a further 2 hours at 50°-55° C.; after cooling, the reaction product which had precipitated was filtered off, washed with 20 liters of water and dried. 4.80 kg (96% of theory) of 4-amino-6-tert.-butyl-3-mercapto-1,2,4-triazin-5(4H)-one (V) were obtained as colorless crystals of melting point 212°-214° C.; content, according to determination by gas chromatography, >99%.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH2:5][CH:6]2[CH2:9][CH:10]=[O:11].[CH3:13][C:14]([CH3:17])([O-])[CH3:15].[K+].C(Cl)C(=C)C>CN(C=O)C>[CH3:1][C:2]1([CH3:12])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH2:5][CH:6]2[CH:9]([CH2:15][C:14]([CH3:17])=[CH2:13])[CH:10]=[O:11]
Reactant: CC1(C)C2CCC(CC=O)C1C2
Reactant: CC(C)(C)[O-]
Agent: C=C(C)CCl
Agent: [K+]
Solvent: CN(C)C=O
Product: C=C(C)CC(C=O)C1CCC2CC1C2(C)C
Yield: 29.6 %

Procedure:
In a manner similar to Example 6, 90 g of 6,6-dimethylbicyclo[3.1.1]hept-2-yl acetaldehyde (0.529 mole) in 40 ml of DMF, 108 g of potassium t-butoxide (0.91 mole) in 400 ml of DMF, and 93 g of methallyl chloride (1.02 moles) in 40 ml of DMF were reacted in the usual manner. After work-up the crude mixture of C- and O-alkylates, 112 g, was heated at 165°-175° C. for 4 hours. The crude product was dwastilled to afford 34.5 g of purified product (30% yield). BP 90° C./0.1 mmHg; 1H-NMR (300 MHz), δ 1.06 (3H, s), 1.16 s), 1.69 (3H, s), 1.3-2.6 (12H, m), 4.67 (1H, s), 4.74 (1H, s), 9.36 (1H, m); 13C-NMR (75 MHz), spectra consistent with assigned structures; IR (Neat) 2960, 2700, 1730, 1650, 1470, 1370, 890 cm-1 ; MS (m/e), 220 (M+), 205, 189, 177, 163, 149, 135, 121, 107, 93, 79, 69, 41 (Base);
Reaction SMILES: [CH2:1]([Si:4]([Cl:7])([Cl:6])[Cl:5])[CH:2]=[CH2:3].[BH3:8]>O1CCCC1>[Cl:5][Si:4]([CH2:1][CH2:2][CH2:3][B:8]([CH2:3][CH2:2][CH2:1][Si:4]([Cl:7])([Cl:6])[Cl:5])[CH2:3][CH2:2][CH2:1][Si:4]([Cl:7])([Cl:6])[Cl:5])([Cl:7])[Cl:6]
Reactant: C=CC[Si](Cl)(Cl)Cl
Reactant: B
Solvent: C1CCOC1
Product: Cl[Si](Cl)(Cl)CCCB(CCC[Si](Cl)(Cl)Cl)CCC[Si](Cl)(Cl)Cl
Temperature: 0 °C
Reaction time: 4 h
Yield: 82 %

Procedure:
The (Cl3SiCH2CH2CH2)3B functional initiator was prepared by hydroboration of allyltrichlorosilane with boron hydride (3:1 mole ratio). Hydroboration reaction was conducted at 0° C. for 4 hours in tetrahydrofuran (THF). In a typical example, the reaction was carried out in dried flask containing 20 ml dried THF and 8.7 ml (0.06 mol) allyltrichlorosilane. The solution was then cooled down to 0° C., and 20 ml (0.02 mol) of 0.1 M boron hydride in THF was then dropped slowly via the air-tight syringe into the reaction flask. The solution was stirred at 0° C. for 4 h. After that the THF was removed under high vacuum pump to obtain about 82% yield tri(trichlorosilyl propyl)borane initiator.