Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:19]([N:20]2[CH2:24][CH2:23][CH2:22][C:21]2=O)=[CH:18][CH:17]=[C:16]([Cl:26])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([CH:12]=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+]>O1CCCC1>[Cl:1][C:2]1[C:19]([N:20]2[CH2:21][CH2:22][CH2:23][CH2:24]2)=[CH:18][CH:17]=[C:16]([Cl:26])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([CH:12]=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: Cc1cn2cccc(OCc3c(Cl)ccc(N4CCCC4=O)c3Cl)c2n1
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Product: Cc1cn2cccc(OCc3c(Cl)ccc(N4CCCC4)c3Cl)c2n1
Reaction time: 2 h
Yield: 19.9 %

Procedure:
To a solution of 8-[2,6-dichloro-3-(2-pyrrolidon-1-yl)benzyloxy]-2-methylimidazo[1,2-a]pyridine (120 mg) in tetrahydrofuran (3 ml) was added lithium aluminum hydride (19 mg) under ice-cooling, and the mixture was stirred for 2 hours. A saturated aqueous ammonium chloride solution was added thereto, and insoluble material was filtered off. The filtrate was concentrated, and the residue was purified by preparative thin-layer chromatography (5% solution of methanol in methylene chloride) to give 8-[2,6-dichloro-3-(1-pyrrolidinyl)benzyloxy]-2-methylimidazo[1,2-a]pyridine (23 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].CS(O[CH2:40][CH:41]=[C:42]1[CH2:51][CH2:50][C:45]2([O:49][CH2:48][CH2:47][O:46]2)[CH2:44][CH2:43]1)(=O)=O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:40][CH:41]=[C:42]3[CH2:51][CH2:50][C:45]4([O:46][CH2:47][CH2:48][O:49]4)[CH2:44][CH2:43]3)[N:9]=2)[CH:7]=1
Reactant: O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1cnn2cccnc12
Reactant: CS(=O)(=O)OCC=C1CCC2(CC1)OCCO2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=C(Nc1cn(CC=C2CCC3(CC2)OCCO3)nc1-c1cc(Cl)ccc1OC(F)F)c1cnn2cccnc12
Temperature: 25 °C
Reaction time: 4 h
Yield: 75.1 %

Procedure:
To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (1.50 g, 3.71 mmol) in N,N-dimethylformamide (120 mL) was added Cs2CO3 (3.62 g, 11.11 mmol) and 2-[1,4-dioxaspiro[4.5]decan-8-ylidene]ethyl methanesulfonate (1.94 g, 7.39 mmol) at room temperature. The resulting solution was stirred for 4 h at room temperature and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (3/2) to give 1.59 g (75%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[1,4-dioxaspiro[4.5]decan-8-ylidene]ethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 31) [M+H]+=571.4, RT=1.21 min.
Reaction SMILES: [CH2:1]([N:8]([CH2:22][CH2:23][NH:24][CH2:25][CH2:26][C:27]1[C:35]2[S:34][C:33](=[O:36])[NH:32][C:31]=2[C:30]([OH:37])=[CH:29][CH:28]=1)[C:9](=O)[CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.[CH3:39]O>O1CCCC1>[OH:37][C:30]1[C:31]2[NH:32][C:33](=[O:36])[S:34][C:35]=2[C:27]([CH2:26][CH2:25][NH:24][CH2:23][CH2:22][N:8]([CH2:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:1][CH2:2][C:7]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:39]=2)=[CH:28][CH:29]=1
Reactant: O=C(CCOCCc1ccccc1)N(CCNCCc1ccc(O)c2[nH]c(=O)sc12)Cc1ccccc1
Reactant: CO
Agent: B
Solvent: C1CCOC1
Product: O=c1[nH]c2c(O)ccc(CCNCCN(CCCOCCc3ccccc3)CCc3ccccc3)c2s1
Temperature: 0 °C

Procedure:
N-Benzyl-N-[2-[2-(4-hydroxy-2-oxo-3H-benzothiazol-7-yl)ethylamino]ethyl]-3-phenethyloxy-propanamide (Example 4, 0.1 g) was dissolved in tetrahydrofuran (6 mL) and treated with borane (1M in tetrahydrofuran, 1 mL) at room temperature. The resultant solution was heated at 50° C. for 3 hours. The reaction was then cooled to 0° C. and methanol (6 mL) was added dropwise. Following this, the mixture was concentrated and the collected residue was dissolved in methanol (6 mL) and treated with concentrated hydrochloric acid (1.6 mL). The acidic solution was heated at 60° C. for 14 hours, then cooled to room temperature and concentrated. The resulting residue was purified by preparative HPLC (95:05, ammonia (0.2%):acetonitrile) to give the titled compound (0.035 g) as a glass like solid.
Reaction SMILES: [CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[Na+].Br[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(Cl)Cl>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[N:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:13][C:14]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]1=2
Reactant: c1ccc2c(c1)Cc1ccccc1N2
Reactant: Brc1ccccn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: c1ccc(N2c3ccccc3Cc3ccccc32)nc1
Reaction time: 18 h
Yield: 87.7 %

Procedure:
A mixture of 10.00 g of acridan (55.2 mmol), 247.7 mg of Pd(OAc)2 (1.10 mmol), 178.6 mg of tri-t-butylphosphine (0.88 mmol), 7.95 g of sodium t-butoxide (82.7 mmol), and 6.3 mL of 2-bromopyridine (66.2 mmol) in 100 mL of dry toluene was allowed to stir under inert atmosphere for 18 h. The reaction mixture was poured into a mixture of 300 mL of CH2Cl2 and 100 g of silica gel with stirring. The mixture was filtered, and the solid material was washed with 1 L of CH2Cl2. The filtrate was concentrated in vacuo to afford a yellow oil, which was taken up in hexanes. The semi-solution was again concentrated in vacuo to afford a yellow solid. The solid was triturated in 100 mL of hexanes for several hours, filtered and dried to afford 12.50 g of N-pyridylacridan (88%).
Reaction SMILES: NC1C=CC=CC=1[N:8]1[C:12](=[O:13])[CH:11]([CH2:14][C:15]([OH:17])=O)[S:10][CH:9]1[NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[2H][C:26]1[C:31]([2H])=[C:30]([NH2:33])[C:29]([NH2:34])=[C:28]([2H])[C:27]=1[2H].Cl.CN(C)CCCN=C=NCC.CC#N>C(Cl)Cl.CN(C=O)C>[NH2:33][C:30]1[CH:31]=[CH:26][CH:27]=[CH:28][C:29]=1[NH:34][C:15](=[O:17])[CH2:14][CH:11]1[S:10][C:9]([NH:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:8][C:12]1=[O:13]
Reactant: Nc1ccccc1N1C(=O)C(CC(=O)O)SC1Nc1ccccc1
Reactant: [2H]c1c([2H])c([2H])c(N)c(N)c1[2H]
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CC#N
Product: Nc1ccccc1NC(=O)CC1SC(Nc2ccccc2)=NC1=O
Temperature: 40 °C
Reaction time: 2 h

Procedure:
N-(2-Aminophenyl)-2-(2-anilino-4-oxo-4,5-dihydro-1,3-thiazol-5-yl)acetic acid, prepared using method 2 above, (30 mg, 1 eq) was dissolved in a mixture of DCM/DMF (2 mL/2 mL) and O-phenylenediamine (15 mg, 1.1 eq), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC, 30 mg, 1.3 eq) were then added sequentially. The reaction mixture was stirred 40° C. for 2 h. Separated between DCM and H2O, the organic layer concentrated to give a crude orange brown oil used directly in the next step: HPLC 43%, RT=0.93 min (System B, 2-95% MeCN over 2 min); MS [M+H]m/z=341.
Reaction SMILES: [F:1][C:2]1[C:3]([CH3:26])=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18]C(=O)OC(C)(C)C)[N:14]=[CH:15]3)=[CH:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.FC(F)(F)C(O)=O>ClCCCl>[F:1][C:2]1[C:3]([CH3:26])=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][N:9]=2)[CH:5]=[N:6][CH:7]=1
Reactant: Cc1c(F)cncc1-c1cc2cnc(NC(=O)OC(C)(C)C)cc2cn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCCl
Product: Cc1c(F)cncc1-c1cc2cnc(N)cc2cn1
Temperature: 40 °C
Reaction time: 3 h
Yield: 101.1 %

Procedure:
A suspension of tert-butyl 7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate (50 mg, 0.14 mmol) in 1,2-dichloroethane (1 mL) was treated with trifluoroacetic acid (0.11 mL, 1.41 mmol), and the mixture was stirred at 40° C. for 3 hours. The mixture was concentrated in vacuo and then diluted with ethyl acetate (50 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford the title compound as a bright yellow solid (36 mg, 98%), which was used in the next step without further purification.
Reaction SMILES: Cl.[C:2]1([C@@H:8]2[CH2:10][C@H:9]2[NH2:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:12][C:13]([F:23])([F:22])[C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.O>[C:2]1([C@@H:8]2[CH2:10][C@H:9]2[NH:11][CH2:18][C:17]2[CH:16]=[CH:15][C:14]([C:13]([F:12])([F:22])[F:23])=[CH:21][CH:20]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N[C@@H]1C[C@H]1c1ccccc1
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: FC(F)(F)c1ccc(CN[C@@H]2C[C@H]2c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 37.9 %

Procedure:
A mixture of (trans)-2-phenylcyclopropanamine hydrochloride (0.23 g, 1.36 mmol) and 4-(trifluoromethyl)benzaldehyde (0.20 mL, 1.49 mmol) in CH2Cl2 (8 mL) and water (0.5 mL) was vigorously stirred at room temperature for 10 min. Then, NaBH(OAc)3 (0.37 g, 1.76 mmol) was slowly added and stirring continued for 30 min. The reaction mixture was washed with an aqueous saturated solution of NaHCO3 (8 mL), the organic layer was dried over anhydrous Na2SO4, filtered and, after removal of the solvent, the residual oil was purified by column chromatography on silica gel (1% MeOH/CH2Cl2) affording 0.15 g of N-[(trans)-2-phenylcyclopropyl]-N-[4-(trifluoromethyl)benzyl]amine [Rf=0.6 (5% MeOH/CH2Cl2), colorless oil, 38% yield].
Reaction SMILES: Cl[C:2]1[N:20]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([N:28]2[CH2:33][CH2:32][N:31]([CH2:34][C@H:35]([OH:37])[CH3:36])[CH2:30][CH2:29]2)[CH:25]=[CH:26][CH:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:19][S:16]([C:13]1[CH:14]=[CH:15][C:10]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:21][C:22]4[CH:23]=[C:24]([N:28]5[CH2:29][CH2:30][N:31]([CH2:34][C@H:35]([OH:37])[CH3:36])[CH2:32][CH2:33]5)[CH:25]=[CH:26][CH:27]=4)[N:20]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:11][CH:12]=1)(=[O:18])=[O:17]
Reactant: CS(=O)(=O)c1ccc(-c2cccn3nc(Cl)nc23)cc1
Reactant: C[C@@H](O)CN1CCN(c2cccc(N)c2)CC1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: C[C@@H](O)CN1CCN(c2cccc(Nc3nc4c(-c5ccc(S(C)(=O)=O)cc5)cccn4n3)c2)CC1

Procedure:
(R)-1-(4-{3-[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-phenyl}-piperazin-1-yl)-propan-2-ol was prepared from 2-chloro-8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (100.0 mg, 0.3249 mmol) and (R)-1-[4-(3-amino-phenyl)-piperazin-1-yl]-propan-2-ol (84.0 mg, 0.357 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (36.0 mg, 0.0658 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a yellow foam (0.105 g, 63%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.49 (d, J=6.4 Hz, 1H), 8.25 (d, J=8.4 Hz, 2H), 8.07 (d, J=8.4 Hz, 2H), 7.66 (d, J=7.3 Hz, 1H), 7.40 (s, 1H), 7.23 (t, J=8.2 Hz, 1H), 7.02 (t, J=7.1 Hz, 1H), 6.98-6.94 (m, 1H), 6.88 (s, 1H), 6.59 (dd, J=8.2, 1.7 Hz, 1H), 3.97-3.87 (m, 1H), 3.33-3.21 (m, 5H), 3.10 (S, 3H), 2.90-2.82 (m, 2H), 2.62-2.55 (m, 2H), 2.43-2.30 (m, 2H), 1.17 (d, J=6.1 Hz, 3H). MS=507 (MH)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:15][C:14](=[O:16])[N:13]([CH3:17])[CH2:12][N:11]=2)=[CH:6][CH:5]=1)([O-])=O.[H][H]>O1CCOCC1.[Pt]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:15][C:14](=[O:16])[N:13]([CH3:17])[CH2:12][N:11]=2)=[CH:8][CH:9]=1
Reactant: CN1CN=C(c2ccc([N+](=O)[O-])cc2)OC1=O
Reactant: [H][H]
Agent: [Pt]
Solvent: C1COCCO1
Product: CN1CN=C(c2ccc(N)cc2)OC1=O

Procedure:
3 g of 6-(4-nitro-phenyl)-3-methyl-3,4-dihydro-2H-1,3,5-oxadiazin-2-one in 60 ml of dioxan are hydrogenated with 0.3 g of platinum/charcoal (5%) as catalyst until the uptake of hydrogen has ceased. The hydrogenation is carried out at room temperature and under normal pressure. The catalyst is then filtered off, the solvent evaporated off in vacuo and the residue is recrystallised from ethyl acetate to yield 6-(4-amino-phenyl)-3-methyl,3,4-dihydro-2H-1,3,5-oxadiazin-2-one which melts at 173°-174°C with decomposition (compound 83).
Reaction SMILES: C([O:7][CH2:8][C@@H:9]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:10]1[C:34]([CH3:35])=[CH:33][C:13]2[N:14]=[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19](C4C=C5C(C=NN5C)=CC=4)[CH:18]=3)[S:16][C:12]=2[C:11]=1[C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)(=O)C(C)(C)C.C(OC[C@@H](OC(C)(C)C)C1C(C)=CC2N=C([C:64]3[CH:65]=[C:66]4[C:70](=[CH:71][CH:72]=3)[N:69]([CH3:73])[N:68]=[CH:67]4)SC=2C=1C1C=CC(Cl)=CC=1)(=O)C(C)(C)C.CO.[OH-].[Na+]>C(OCC)(=O)C>[C:44]([O:43][C@@H:9]([C:10]1[C:34]([CH3:35])=[CH:33][C:13]2[N:14]=[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:64]4[CH:65]=[C:66]5[C:70](=[CH:71][CH:72]=4)[N:69]([CH3:73])[N:68]=[CH:67]5)[CH:18]=3)[S:16][C:12]=2[C:11]=1[C:36]1[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][CH:41]=1)[CH2:8][OH:7])([CH3:46])([CH3:47])[CH3:45]
Reactant: Cc1cc2nc(-c3ccnc(-c4ccc5cnn(C)c5c4)c3)sc2c(-c2ccc(Cl)cc2)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Reactant: Cc1cc2nc(-c3ccc4c(cnn4C)c3)sc2c(-c2ccc(Cl)cc2)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1cc2nc(-c3ccnc(-c4ccc5c(cnn5C)c4)c3)sc2c(-c2ccc(Cl)cc2)c1[C@@H](CO)OC(C)(C)C
Temperature: 55 °C

Procedure:
(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-6-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)ethyl pivalate and (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-indazol-5-yl)benzo[d]thiazol-6-yl)ethyl pivalate was telescoped into the subsequent reaction. To the previous reaction mixture, methanol and 2M NaOH were added and reaction mixture was heated at 55° C. overnight. Reaction mixture was cooled to rt, diluted with ethyl acetate and washed with brine. The organic layer was dried (MgSO4), filtered, concentrated and purified by CombiFlash (Hex/EtOAc) to give (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-5-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)ethanol. LCMS-ESI+: calc'd for C33H32ClN4O2S: 583.2 (M+H+); found: 583.2 (M+H+).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([SiH2:15][O:16][C:17]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:18]1[CH2:22][CH2:21][C:20]([CH2:24][OH:25])([CH3:23])[C:19]1([CH3:27])[CH3:26])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.O>[C:11]([SiH2:15][O:16][C:17]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:18]1[CH2:22][CH2:21][C:20]([CH3:23])([CH:24]=[O:25])[C:19]1([CH3:27])[CH3:26])([CH3:12])([CH3:13])[CH3:14]
Reactant: CC(C)(C)[SiH2]OC(c1ccccc1)(c1ccccc1)C1CCC(C)(CO)C1(C)C
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)[SiH2]OC(c1ccccc1)(c1ccccc1)C1CCC(C)(C=O)C1(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 96.6 %

Procedure:
To a solution of oxalyl chloride (0.977 mL, 11.2 mmol) in dry CH2Cl2 (20 mL) at −78° C. was added dropwise DMSO (1.19 mL, 16.8 mmol) in dry CH2Cl2 (2.0 mL) over a period of 10 minutes and the mixture was stirred at −78° C. for 15 minutes. A solution of [3-(tert-butyl-diphenyl-silanyloxymethyl)-1,2,2-trimethyl-cyclopentyl]-methanol (2) (2.30 g, 5.6 mmol) in dry CH2Cl2 (6.0 mL) was added dropwise at −78° C. over a period of 30 minutes and the reaction mixture was stirred at −78° C. for 30 minutes. Triethylamine (3.9 mL, 28.0 mmol) was added dropwise at −78° C. over a period of 10 minutes and the reaction mixture was stirred at −78° C. for 1 hour. The temperature of the mixture is allowed to rise to −10° C. over a period of 3.5 hours and cold H2O (60 mL) was added. The organic layer was separated, the aqueous layer was extracted with Et2O (3×60 mL) and the combined organic layers were dried over anhydrous MgSO4. The solvents were removed in vacuo and the residue was purified over silica (n-hexane/ ethyl acetate, 98:2) to afford 2.21 g (97% yield) of the desired product (4) as a viscous oil which was characterized as follows:
Reaction SMILES: [NH2:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[F:36].N1C=CC=CC=1.Cl[C:44]([O:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:45]>O1CCCC1>[C:17]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH2:20][CH:21]1[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:25][CH2:26]1)[N:10]=[CH:9][CH:8]=[C:7]2[O:6][C:5]1[CH:34]=[CH:35][C:2]([NH:1][C:44]([O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:45])=[C:3]([F:36])[CH:4]=1)#[N:18]
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(COc2cc3nccc(Oc4ccc(N)c(F)c4)c3cc2C#N)CC1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCC(COc2cc3nccc(Oc4ccc(NC(=O)Oc5ccccc5)c(F)c4)c3cc2C#N)CC1
Reaction time: 0.25 h

Procedure:
tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate (523 mg), pyridine (0.17 ml) and tetrahydrofuran (10 ml) were stirred while cooling on ice, and then phenyl chloroformate was added dropwise. Immediately after completion of the dropwise addition, the cooling bath was removed and the mixture was returned to room temperature. After 15 minutes of stirring, water and ethyl acetate were added for extraction. Silica gel was added to the extract and the solvent was distilled off under reduced pressure for adsorption. The reaction solution-adsorbed silica gel was purified by column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, ethyl acetate) in a dry column packed with silica gel, to obtain 490 mg of a yellow powder.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=2)[CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].F[C:19]1[N:24]=[C:23]([C:25]#[N:26])[CH:22]=[CH:21][CH:20]=1>CN(C=O)C.CCOC(C)=O>[N:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:4]1[CH:5]=[N:1][N:2]([C:19]2[N:24]=[C:23]([C:25]#[N:26])[CH:22]=[CH:21][CH:20]=2)[CH:3]=1
Reactant: N#Cc1cccc(F)n1
Reactant: c1ccc(-c2cn[nH]c2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1cccc(-n2cc(-c3ccccn3)cn2)n1
Temperature: 140 °C

Procedure:
2-(1H-Pyrazol-4-yl)pyridine (300 mg, 2.0 mmol) was dissolved in DMF (10 mL), potassium carbonate (566 mg, 4 mmol) and 6-fluoropyridine-2-carbonitrile (250 mg, 2 mmol) was added. The reaction was heated at 140° C. for 16 h. The crude mixture was cooled to rt and diluted with EtOAc (300 mL) and washed with H2O (200 mL) and brine (200 mL). The organic phase was dried (MgSO4), filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexanes:EtOAc (7:3) to afford 6-(4-pyridin-2-yl-1H-pyrazol-1-yl)pyridine-2-carbonitrile. This material was dissolved in methylene chloride (5 mL) and, upon treatment with 1M HCl in diethyl ether (0.6 mL), precipitated as the hydrochloride salt. M.P. 260-261° C. 1H-NMR (CDCl3, 300 MHz) δ 9.67 (s, 1H), 8.83 (s, 1H), 8.79-8.77 (d, J=6 Hz, 1H), 8.47-8.29 (m, 4H), 8.13-8.10 (m, 1H) 7.77-7.73 (t, 1H). MS ESI) 249 (M++H).
Reaction SMILES: [CH2:1]([N:4]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:5][CH2:6][CH2:7][N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:9]/[CH:10]=[CH:11]/[CH2:12][N:13]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:2]=[CH2:3].[H-].[Na+].[CH2:48](I)[CH3:49]>CN(C=O)C>[CH2:1]([N:4]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:5][CH2:6][CH2:7][N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:9]/[CH:10]=[CH:11]/[CH2:12][N:13]([C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[CH2:14][CH2:15][CH2:16][N:17]([CH2:48][CH3:49])[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH:2]=[CH2:3]
Reactant: C=CCN(CCCN(C/C=C/CN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCN(CCCN(C/C=C/CN(CCCN(CC)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C

Procedure:
To a solution of 0.272 g (0.424 mmol) of (E)-1-allyl-1,5,10,14-tetra-BOC-1,5,10,14-tetraazatetradec-7-ene (see Example 2a) in 4 ml of DMF there are added, with stirring, 0.034 g (0.85 mmol) of sodium hydride dispersion (approx. 60%) and, after 5 min., 0.069 ml (0.85 mmol) of ethyl iodide. The reaction mixture is stirred for 15 h at room temperature; a further 0.017 g (0.425 mmol) of sodium hydride dispersion (approx. 60%) and 0.034 ml (0.421 mmol) of ethyl iodide are added, and the mixture is stirred for a further 96 h at 20° C. and is then concentrated by evaporation in vacuo. Working up analogously to Example 1a), but using ethyl acetate-hexane (1:2) in the flash chromatography, yields the title compound, Rf value=0.53 (silica gel/ethyl acetate:hexane (1:1)).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[C:11]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:25][C:26]([NH2:28])=[O:27])(=[O:24])=[O:23])=[CH:18][CH:17]=1)=[O:12].[CH2:29](N)[CH2:30][CH2:31][CH3:32]>O1CCOCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[C:11]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:25][C:26]([NH:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:27])(=[O:24])=[O:23])=[CH:18][CH:17]=1)=[O:12]
Reactant: NC(=O)NS(=O)(=O)c1ccc(CCNC(=O)N2Cc3ccccc3C2=O)cc1
Reactant: CCCCN
Solvent: C1COCCO1
Product: CCCCNC(=O)NS(=O)(=O)c1ccc(CCNC(=O)N2Cc3ccccc3C2=O)cc1

Procedure:
4 g of N-(4-[2-(-1-oxo-isoindoline-2-carboxamido)ethyl]-benzenesulfonyl-urea (melting point 207°-209° C., prepared from 4-[2-(1-oxo-isoindoline-2-carboxamido)-ethyl]-benzenesulfonamide and potassium cyanate in 80% ethanol) and 0.73 g of butylamine in 100 ml of dioxane are refluxed for 1 hour. The solvent is then distilled off under reduced pressure, the residue is reprecipitated from very dilute ammonia and recrystallized from dilute acetone. The N-(4-[2-(1-oxo-isoindoline-2-carboxamido)-ethyl]-benzenesulfonyl)-N'-butyl urea obtained melts at 188° to 190° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH2:9][S:10][CH2:11][CH2:12][NH2:13])=[N:5][CH:6]=[CH:7][CH:8]=1.[N+:14]([CH:17]=[C:18](SC)[S:19]([CH3:21])=O)([O-:16])=[O:15]>CO>[N+:14]([CH:17]=[C:18]([S:19][CH3:21])[NH:13][CH2:12][CH2:11][S:10][CH2:9][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][N:5]=1)([O-:16])=[O:15]
Reactant: CSC(=C[N+](=O)[O-])S(C)=O
Reactant: COc1cccnc1CSCCN
Solvent: CO
Product: COc1cccnc1CSCCNC(=C[N+](=O)[O-])SC
Yield: 56.9 %

Procedure:
A solution of 2-(3-methoxy-2-pyridylmethylthio)ethylamine (2.1g) in methanol (33 ml) was added over 25 minutes to a stirred solution of 1-nitro-2-methylthio-2-methylsulphinylethylene (2.1g) in methanol (75 ml) at 30°. After standing for an hour the solution was concentrated to give a yellow-brown oil which was crystallised from ethanol/ether to yield 1-nitro-2-methylthio-2-[2-(3-methoxy-2-pyridylmethylthio)ethylamino]ethylene (1.9g), m.p. 87.5-88.5°.