Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[N:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH:30][C:31](=[O:47])[C:32]2[CH:37]=[CH:36][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:34][CH:33]=2)=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.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>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:35]3[CH:36]=[CH:37][C:32]([C:31]([NH:30][CH2:29][CH2:28][C:25]4[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=4)=[O:47])=[CH:33][CH:34]=3)[N:3]=2)[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]
Reactant: CC1(C)OB(c2ccc(C(=O)NCCc3ccncc3)cc2)OC1(C)C
Reactant: COc1ccc(Nc2nc(Cl)nc3scnc23)cc1OC
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: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(Nc2nc(-c3ccc(C(=O)NCCc4ccncc4)cc3)nc3scnc23)cc1OC
Yield: 31.5 %

Procedure:
To a stirred solution of 5-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (100 mg, 0.31 mmol) and N-(2-(pyridin-4-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (140 mg, 0.4 mmol) in 25 mL of 1,4-dioxane were added Na2CO3 (64 mg, 0.6 mmol) and 3 mL of water at room temperature. Then the mixture was degassed with nitrogen for 15 minutes. Pd(PPh3)4 (20 mg, 0.017 mmol) was added in one portion and the reaction mixture was stirred at reflux for 16 hours under nitrogen. The solvent was evaporated and the residue was purified by silica gel chromatography (200-300 mesh, eluting with EtOAc) to give 4-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide (50 mg, 31%) as a yellow sold. 1H NMR (300 MHz, DMSO): δ 10.15 (s, 1H), 9.37 (s, 1H), 8.68 (t, 1H, J=5.3 Hz), 8.46-8.42 (m, 4H), 7.94-7.91 (m, 2H), 7.81 (d, 1H, J=2.7 Hz), 7.52-7.47 (m, 1H), 7.27-7.26 (m, 2H), 7.00 (d, 1H, J=8.7 Hz), 4.02 (s, 3H), 4.00 (s, 3H), 3.58-3.52 (m, 2H), 2.89 (t, 2H, J=7.0 Hz). LC-MS: 513 [M+H]+, 511 [M−H]−, tR=1.32 min. HPLC: 97.72% at 214 nm, 96.31% at 254 nm, tR=4.19 min.
Reaction SMILES: [F:1][C:2](=[C:10]([F:12])[F:11])[CH2:3][CH2:4][CH:5]([C:8]#[N:9])[C:6]#[N:7].[H-].[Na+].Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1>CN(C)C=O>[C:23]([C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:5]([CH2:4][CH2:3][C:2]([F:1])=[C:10]([F:11])[F:12])([C:6]#[N:7])[C:8]#[N:9])=[CH:18][CH:19]=1)#[N:24]
Reactant: N#CC(C#N)CCC(F)=C(F)F
Reactant: N#Cc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1ccc(CC(C#N)(C#N)CCC(F)=C(F)F)cc1
Yield: 63.2 %

Procedure:
Using 0.20 g of (3,4,4-trifluoro-3-butenyl)malononitrile, 5 ml of N,N-dimethylformamide, 50 mg of sodium hydride (60% in oil), and 0.25 g of α-bromo-p-tolunitrile, and according to the process described in the Production Example 1, there was obtained 0.21 g of 2-(4-cyanobenzyl)-2-(3,4,4-trifluoro-3-butenyl)malononitrile (the present compound (68)).
Reaction SMILES: P(Br)(Br)[Br:2].[CH2:5]([O:12][C:13]1[C:18]([Cl:19])=[CH:17][C:16]([CH2:20]O)=[CH:15][C:14]=1[Cl:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>ClCCl.C(OCC)C>[CH2:5]([O:12][C:13]1[C:18]([Cl:19])=[CH:17][C:16]([CH2:20][Br:2])=[CH:15][C:14]=1[Cl:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: BrP(Br)Br
Reactant: OCc1cc(Cl)c(OCc2ccccc2)c(Cl)c1
Solvent: CCOCC
Solvent: ClCCl
Product: Clc1cc(CBr)cc(Cl)c1OCc1ccccc1
Reaction time: 2 h

Procedure:
Phosphorous tribromide (2 mL) was added to a solution of (4-benzyloxy-3,5-dichlorophenyl)-methanol (CAB02117, 5.50 g, 19.4 mmol) in dichloromethane (80 mL) at 0° C. The mixture was stirred at this temperature for 2 h, diluted with diethyl ether (150 mL), transferred into a separation funnel and washed with water (2×50 mL) and brine (50 mL). The organic layer was dried over magnesium sulphate and concentrated under reduced pressure. The residue was recrystallised from dichloromethane/hexane. 1H-NMR (400 MHz, CDCl3) δ=4.39 (s, 2H, —CH2Br), 5.05 (s, 2H, —CH2Ph), 7.37 (s, 2H), 7.38-7.44 (m, 3H), 7.54-7.58 (m, 2H). 13C-NMR (100 MHz, CDCl3) δ=31.48, 75.39, 128.73, 129.68, 129.70, 129.72, 130.06, 135.46, 136.27, 151.23.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:18]#[N:19])[CH:15]=2)[NH:10][CH2:9]1)(C)(C)C.[ClH:21].O1CCOCC1>C(Cl)Cl>[ClH:21].[ClH:21].[NH2:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:18]#[N:19])[CH:15]=2)[NH:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)NC1CNc2ccc(C#N)cc2C1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: N#Cc1ccc2c(c1)CC(N)CN2
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
To a solution of 1C (546 mg, 2 mmol) in CH2Cl2 (5 mL) at 0° C. was added 4 M HCl in dioxane (4 mL, 16 mmol). After addition, the reaction mixture was stirred at RT for 2 h, then concentrated. The residue was stripped with ether (3×), and the resulting off-white solid dried in vacuo to afford the title compound (490 mg, 100%).
Reaction SMILES: [C:1]1(=[O:7])[NH:5][C:4](=[O:6])[CH2:3][CH2:2]1.[C:8](Cl)(=[O:17])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].Cl>N1C=CC=CC=1>[C:8]([N:5]1[C:4](=[O:6])[CH2:3][CH2:2][C:1]1=[O:7])(=[O:17])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCC(=O)Cl
Reactant: O=C1CCC(=O)N1
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCCCCC(=O)N1C(=O)CCC1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 65.4 %

Procedure:
20 g succinimide were suspended in 100 ml pyridine, 0.5 g N,N-dimethylaminopyridine added, and 39.2 g nonanoic acid chloride added dropwise at ice-bath temperature. Subsequently the mixture was stirred for 1 h at room temperature and 500 ml of 2N HCl solution were added with cooling. The aqueous phase was extracted with ethyl acetate and the organic phase washed with 2N HCl solution and dried (Na2SO4). After removing the solvent, the residue was twice recrystallized from n-hexane. 31.6 g (65%) N-nonanoylsuccinimide were obtained as a colourless solid. Melting point: 59 to 60° C. (n-hexane). The 1H-NMR spectroscopic data are in agreement with the structure.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]([C:12]#[N:13])[C:5]2=O.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH3:1])[N:3]=2)[N:8]=[CH:7][C:6]=1[C:12]#[N:13]
Reactant: Cc1ccc2[nH]cc(C#N)c(=O)c2n1
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1ccc2ncc(C#N)c(Cl)c2n1
Temperature: 25 °C
Yield: 57.1 %

Procedure:
The suspension of 6-methyl-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carbonitrile (1.47 g, 7.93 mmol) in POCl3 (25 mL) was heated under refluxing for 2 hrs. After cooling to room temperature, the reaction mixture was quenched with ice water and basified with NH4OH followed by extraction with AcOEt. The organic layer was washed with brine and dried over NaSO4, and concentrated to give 4-chloro-6-methyl-[1,5]naphthyridine-3-carbonitrile as a brown solid (0.92 g, 57.1%). HR-MS-EI (+) m/e calcd for C10H6ClN3 (M+) 203.0250. found 203.0252.
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:18])[C:15](=[O:17])[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].[OH-].[Na+].[BrH:25]>O>[Br:25][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:18])[C:15](=[O:17])[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: Br
Reactant: CC(=O)N(C)C1CCN(c2ccc(N)cc2)CC1
Agent: O=N[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)N(C)C1CCN(c2ccc(Br)cc2)CC1
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
To a solution of N-(1-(4-aminophenyl)piperidin-4-yl)-N-methylacetamide (479.7 mg, 1.94 mmol) in 6 mL of aq HBr was added a solution of NaNO2 (147 mg, 2.13 mmol) in 2 mL of H2O at 0° C., then the mixture was stirred at 0° C. for 40 minutes. After that, the mixture was poured into a solution of CuBr (584 mg, 4.07 mmol) in 6 mL aq HBr at 0° C., the reaction was heated to 60° C. and stirred for 2 hours. After cooling, the mixture was based with 2M NaOH to pH=8-9 and extracted with EA, washed with H2O and brine, dried and concentrated to give black solid. MS (m/z): 313 (M+H)+
Reaction SMILES: [CH2:1]([O:3][C:4](=[N:6][O:7][CH2:8][CH2:9][N:10]([CH3:30])[CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[C:26]3[N:25]=[CH:24][N:23]=[C:21]([NH2:22])[C:20]=3[N:19]=[C:18]2C)[C@H:14]([OH:28])[C@@H:13]1[OH:29])[CH3:5])[CH3:2].[CH3:31][NH:32]C[C@H]1O[C@@H](N2C3N=CN=C(N)C=3N=C2NC)[C@H](O)[C@@H]1O.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:3][C:4](=[N:6][O:7][CH2:8][CH2:9][N:10]([CH3:30])[CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[C:26]3[N:25]=[CH:24][N:23]=[C:21]([NH2:22])[C:20]=3[N:19]=[C:18]2[NH:32][CH3:31])[C@H:14]([OH:28])[C@@H:13]1[OH:29])[CH3:5])[CH3:2]
Reactant: CNC[C@H]1O[C@@H](n2c(NC)nc3c(N)ncnc32)[C@H](O)[C@@H]1O
Reactant: CCOC(C)=NOCCN(C)C[C@H]1O[C@@H](n2c(C)nc3c(N)ncnc32)[C@H](O)[C@@H]1O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(C)=NOCCN(C)C[C@H]1O[C@@H](n2c(NC)nc3c(N)ncnc32)[C@H](O)[C@@H]1O

Procedure:
Compound 6b was prepared by the same procedure as reported for 6a using 4c (500 mg, 1.61 mmol), ethyl N-(2-bromoethoxy)ethanamidate48 (407 mg, 1.93 mmol), DIEA (104 mg, 0.14 mL, 0.80 mmol), and DMF (5 mL). After column chromatography (elution with 7:1:0.3 chloroform:methanol:NH4OH), a yellow glassy sticky solid was obtained: yield 209 mg (30%), MS: m/z 439 (M+H)+; 1HNMR (DMSO-d6) δ 7.89 (s, 1H, H-2), 6.85 (q, 1H, 8CH3—NH), 6.47 (bs, 2H, 6-NH2), 5.69 (d, 1H, H-1′, J1′,2′=5.0 Hz), 5.27 (d, 1H, 2′-OH, J2′-2′OH=5.5 Hz), 5.06 (d, 1H, 3′-OH, J3′-3′OH=5.0 Hz), 4.88 (ddd, 1H, H-2′, J1′,2′=5.0 Hz, J2′,3′=5.8 Hz, J2′-2′OH=5.5 Hz), 4.17 (ddd, 1H, H-3′, J2′,3′=5.8 Hz, J3′,4′=4.7 Hz, J3′-3′OH=5.0 Hz), 3.86-3.95 (m, 3H, H-4′, NO—CH2), 3.92 (q, 2H, CH2CH3), 2.88 (d, 3H, 8NH—CH3, J=4.6 Hz), 2.71-2.77 (m, 1H, 5′-CH2), 2.56-2.67 (m, 3H, 5′-CH2, N(CH3)—CH2), 2.24 (s, 3H, N—CH3), 1.83 (s, 3H, C—CH3), 1.19 (t, 3H, OCH2CH3).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14](O)=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1.C(Cl)(=O)C(Cl)=O.Cl.CN.[CH2:27]([N:29](CC)CC)C>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH:29][CH3:27])=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1
Reactant: CCN(CC)CC
Reactant: O=C(O)c1cnccc1-c1ccc(Cl)cc1F
Agent: CN
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CNC(=O)c1cnccc1-c1ccc(Cl)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 62 %

Procedure:
To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (2 g, 7.95 mmol in dichloromethane (40 mL) cooled to 0° C. was added oxalyl chloride (2.09 mL, 23.8 mmol) followed by DMF (2 mL). The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane (25 mL). This solution was added to a mixture of methylamine hydrochloride (5.37 g, 79 mmol) and triethylamine (11.08 mL, 79 mmol) in dichloromethane (25 mL) cooled to 0° C. The resultant mixture was stirred at room temperature for 3 h and then washed with a saturated solution of sodium bicarbonate. The organic layer was separated, dried (Na2SO4) and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-N-methylnicotinamide (1.3 g, 4.91 mmol, 62%) as an off-white solid. LC/MS (ESI) m/e 265.1 [(M+H)+, calcd for C13H11ClFN2O 265.1]; LC/MS retention time (method C): tR=1.69 min.
Reaction SMILES: Br[C:2]1[N:6]2[C:7]3[C:12]([N:13]=[C:14]([CH3:15])[C:5]2=[C:4]([CH3:17])[N:3]=1)=[CH:11][CH:10]=[C:9]([F:16])[CH:8]=3.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>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>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1[C:2]1[N:6]2[C:7]3[C:12]([N:13]=[C:14]([CH3:15])[C:5]2=[C:4]([CH3:17])[N:3]=1)=[CH:11][CH:10]=[C:9]([F:16])[CH:8]=3
Reactant: OB(O)c1cc(Cl)ccc1Cl
Reactant: Cc1nc(Br)n2c1c(C)nc1ccc(F)cc12
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+]
Product: Cc1nc(-c2cc(Cl)ccc2Cl)n2c1c(C)nc1ccc(F)cc12
Yield: 25.5 %

Procedure:
Following the general Suzuki coupling procedure, reaction of bromide 5A (75 mg, 0.25 mmol), 2,5-dichlorophenylboronic acid (58 mg, 0.30 mmol), K2CO3 (105 mg, 0.75 mmol) and Pd(PPh3)4 (5.8 mg, 0.005 mmol) provided the coupling product as a white powder (23 mg, 25% yield). EIMS 360.0 [M+H]+.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([C:14]3[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:15]=3[O:16][CH2:17][CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH:11][N:10]=2)=[N:6][CH:7]=1.[CH3:34][N:35](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[C:34]([C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([C:14]3[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:15]=3[O:16][CH2:17][CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[NH:11][N:10]=2)=[N:6][CH:7]=1)#[N:35]
Reactant: COc1cccc(OCCCNC(=O)OC(C)(C)C)c1-c1cc(Nc2cnc(Br)cn2)n[nH]1
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: COc1cccc(OCCCNC(=O)OC(C)(C)C)c1-c1cc(Nc2cnc(C#N)cn2)n[nH]1
Temperature: 80 °C
Yield: 73 %

Procedure:
A solution of tert-butyl 3-(2-(3-(5-bromopyrazin-2-ylamino)-1H-pyrazol-5-yl)-3-methoxyphenoxy)propylcarbamate (0.378 g, 0.730 mmol) and zinc cyanide (0.10 g, 0.870 mmol) in DMF (10 mL) is degassed with a stream of nitrogen for one hour and then heated to 80° C. To the reaction is added Pd(Ph3P)4 (0.080 g, 0.070 mmol), and the mixture is heated overnight. The reaction is cooled to room temperature and concentrated under reduced pressure. The residue is purified by silica gel chromatography (CH2Cl2/MeOH) to give 0.251 g (73%) of the title compound.
Reaction SMILES: [NH:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[NH:11])[NH:3]1.C1(C2CCCCCCCCCC=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][NH:14]N=1>[Ni](Cl)Cl.CO>[CH:8]1[CH:7]=[CH:6][C:5]2[C:10](=[C:2]3[N:1]=[C:15]4[N:14]=[C:22]([C:21]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=54)[N:11]=[C:4]4[NH:3][C:2]([C:10]5[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=54)=[N:1][C:15]4=[N:14][C:22]([C:21]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=54)=[N:11][C:4]=2[NH:3]3)[CH:9]=1
Reactant: N=C1NC(=N)c2ccccc21
Reactant: C1=C(C2=NNCCCCCCCC2)CCCCCCCCC1
Agent: Cl[Ni]Cl
Solvent: CO
Product: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Temperature: 25 °C
Yield: 28.5 %

Procedure:
In 20 g of n-amylalcohol were dissolved 10 g (0.02865 mole) of the diiminoisoindoline of the formula (XXXII) and 4.36 g (0.02863 mole) of diazabicycloundecene, to which 0.92 g (0.0071 mole) of nickel chloride was added. The mixture was then heated under reflux for 30 hours. The reaction mixture was then cooled to room temperature and poured into 120 ml of methanol. The crystals thus precipitated were washed with a small amount of methanol and the resulting crystals were purified with a chloroform/THF (=9/1 (weight ratio))/silica gel column to obtain 2.1 g (yield: 25.2%) of a phthalocyanine compound of the formula (XXIII) below. This compound showed max in toluene of 749 nm and logC- of 5.10. The IR spectrum of this compound is shown in FIG. 9. ##STR54##
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:11]O>C(O)(=O)C>[CH3:2][C:1]([C:5]1[CH:10]=[CH:9][N+:8]([O-:11])=[CH:7][CH:6]=1)([CH3:4])[CH3:3]
Reactant: OO
Reactant: CC(C)(C)c1ccncc1
Solvent: CC(=O)O
Product: CC(C)(C)c1cc[n+]([O-])cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of 4-tert-butylpyridine (19.0 g) in acetic acid (90 ml) was added dropwise 50% of hydrogen peroxide aqueous solution (20 ml) at room temperature and stirred for 30 minutes under the same condition. The mixture was stirred for 3 hours at ca.80° C. After cooling to room temperature, to the mixture was added dropwise another 20 ml of 50% hydrogen peroxide aqueous solution and stirred for 30 minutes. The mixture was stirred for 3 hours at ca. 80° C. After cooling to room temperature, the mixture was concentrated in vacuo. The residue was taken up with chloroform, and washed with water (50 ml), saturated sodium carbonate aqueous solution (50 ml) and water (50 ml). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give 4-tert-butyl-1-oxypyridine, which was crystallized by isopropyl ether as a colorless powder (19.1 g).
Reaction SMILES: C([NH:4][C:5]1[C:6]2[C:13](Br)=[CH:12][N:11]([C@@H:15]3[O:27][C@H:26]([CH2:28][O:29]C(=O)C)[C@@H:21]([O:22]C(=O)C)[C@@:16]3([CH3:33])[O:17]C(=O)C)[C:7]=2[N:8]=[CH:9][N:10]=1)(=O)C.C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:49])(=O)=O)=CC=1.[Cl-].[NH4+]>C1COCC1.ClCCl>[NH2:4][C:5]1[C:6]2[C:13]([F:49])=[CH:12][N:11]([C@@H:15]3[O:27][C@H:26]([CH2:28][OH:29])[C@@H:21]([OH:22])[C@@:16]3([CH3:33])[OH:17])[C:7]=2[N:8]=[CH:9][N:10]=1
Reactant: CC(=O)Nc1ncnc2c1c(Br)cn2[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@@]1(C)OC(C)=O
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1cc(F)c2c(N)ncnc21
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a pre-cooled (−78° C.) solution of the compound from Step B (529 mg, 1.00 mmol) in THF is added butyl lithium (2M in hexanes) (0.5 mL, 1.00 mmol). The resulting solution is stirred at −78° C. for 30 min and then quenched with N-fluorobenzensulfonimide (315 mg, 1.00 mmol) in THF. The resulting solution is very slowly allowed to come to ambient temperature and then poured into a stirred mixture of saturated aqueous ammonium chloride and dichloromethane. The organic phase is evaporated in vacuo and treated with ammonium hydroxide at 55° C. in a closed container overnight. The resulting crude mixture is purified on silica gel using dichloromethane/methanol as the eluent. Fractions containing the desired product are pooled and evaporated in vacuo to give the desired product.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH3:9][O:10][C:11](=[O:22])[CH2:12][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH3:14].Br[CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27]>C1COCC1>[CH3:9][O:10][C:11](=[O:22])[CH:12]([CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27])[N:13]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH3:14]
Reactant: CC(C)=CCBr
Reactant: COC(=O)CN(C)C(=O)OC(C)(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C(CC=C(C)C)N(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63.7 %

Procedure:
A 2 M solution of LDA (70.32 ml, 0.14 mol) was added (via syringe) to a solution of N-t-butoxycarbonyl-sarcosine methyl ester (26 g, 0.1279 mol) in 40 ml of dry THF at -78° C. under nitrogen and the mixture was stirred at this temperature for 30 minutes. To the above mixture was added 4-bromo-2-methyl-2-butene (20 g, 0.134 mol) with stirring continuing at -78° C., and the resulting mixture was allowed to warm to room temperature. The reaction mixture was quenched with 6 ml of saturated ammonium chloride solution at -78° C., 20 ml of water added, and the resulting reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, and concentrated in vacuo to yield a yellow oil, which was purified by silica gel column chromatography (20% ethyl acetate in hexane) to afford 22.1 g (63.7 %) of N-t-butoxycarbonyl-2-(3-methyl-2-butenyl)-sarcosine methyl ester as an oil.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[CH3:13][N:14]([CH2:16][CH2:17][C@@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:28])[CH:24]=2)[CH2:19]1)[CH3:15].[CH3:29][O:30][C:31]1[CH:47]=[CH:46][C:34]([C:35]([O:37][C:38]2[CH:43]=[CH:42][C:41]([CH2:44]O)=[CH:40][CH:39]=2)=[O:36])=[CH:33][CH:32]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:13][N:14]([CH2:16][CH2:17][C@@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:28][CH2:44][C:41]3[CH:40]=[CH:39][C:38]([O:37][C:35]([C:34]4[CH:33]=[CH:32][C:31]([O:30][CH3:29])=[CH:47][CH:46]=4)=[O:36])=[CH:43][CH:42]=3)[CH:24]=2)[CH2:19]1)[CH3:15]
Reactant: COc1ccc(C(=O)Oc2ccc(CO)cc2)cc1
Reactant: CN(C)CC[C@@H]1CCc2cc(O)ccc2C1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc(C(=O)Oc2ccc(COc3ccc4c(c3)CC[C@@H](CCN(C)C)C4)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 50.9 %

Procedure:
Diethyl azodicarboxylate (40% toluene solution, 0.95 g) was added dropwise to THF solution (6 ml) of 2-(R)-[2-(N,N-dimethylamino)ethyl]-6-hydroxytetralin (300 mg), 4-(hydroxymethyl)phenyl 4-methoxybenzoate (530 mg), and triphenylphosphine (430 mg) under ice-cooling. After stirring for 2 hours at room temperature, the reaction mixture was concentrated. The residue was purified using alumina column chromatography (development solvent; hexane˜hexane:ethyl acetate=10:1), and the titled compound (320 mg) was obtained after recrystallization (ethyl acetate-hexane).
Reaction SMILES: C(O)(=O)C.[C:5]([N:9]([CH3:35])[C:10]([C:12]1[N:16]2[CH2:17][CH2:18][C:19]3[C:24]([C:15]2=[C:14]([C:30]2[S:31][CH:32]=[CH:33][CH:34]=2)[CH:13]=1)=[CH:23][C:22]([N+:25]([O-])=O)=[C:21]([O:28][CH3:29])[CH:20]=3)=[O:11])([CH3:8])([CH3:7])[CH3:6]>C1COCC1.[Zn]>[C:5]([N:9]([CH3:35])[C:10]([C:12]1[N:16]2[CH2:17][CH2:18][C:19]3[C:24]([C:15]2=[C:14]([C:30]2[S:31][CH:32]=[CH:33][CH:34]=2)[CH:13]=1)=[CH:23][C:22]([NH2:25])=[C:21]([O:28][CH3:29])[CH:20]=3)=[O:11])([CH3:7])([CH3:8])[CH3:6]
Reactant: COc1cc2c(cc1[N+](=O)[O-])-c1c(-c3cccs3)cc(C(=O)N(C)C(C)(C)C)n1CC2
Agent: [Zn]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COc1cc2c(cc1N)-c1c(-c3cccs3)cc(C(=O)N(C)C(C)(C)C)n1CC2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Acetic acid (0.39 ml) was added portionwise to a solution of the product of example 94 (300 mg) in THF (10 ml) at 0° C., followed by the portionwise addition of zinc (893 mg). After stirring for 2 h at room temperature, the reaction mixture was filtered over decalite. The filtrate was concentrated in vacuo and dissolved in ethyl acetate. The organic layer was washed with saturated NaHCO3 solution and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Residue was purified by preparative HPLC (0→100% acetonitrile; system 1).
Reaction SMILES: [NH2:1][CH:2]1[CH:6]([CH2:7][NH2:8])[C:5]([CH3:10])([CH3:9])[CH2:4][CH:3]1[CH3:11].[CH3:12][C:13]1[O:19]C(C)(C)[O:17][C:15](=O)[CH:14]=1>C1(C)C(C)=CC=CC=1>[C:15]([NH:1][CH:2]1[CH:3]([CH3:11])[CH2:4][C:5]([CH3:10])([CH3:9])[CH:6]1[CH2:7][NH:8][C:15](=[O:17])[CH2:14][C:13]([CH3:12])=[O:19])(=[O:17])[CH2:14][C:13]([CH3:12])=[O:19]
Reactant: CC1CC(C)(C)C(CN)C1N
Reactant: CC1=CC(=O)OC(C)(C)O1
Solvent: Cc1ccccc1C
Product: CC(=O)CC(=O)NCC1C(NC(=O)CC(C)=O)C(C)CC1(C)C
Temperature: 113 °C
Yield: 89.3 %

Procedure:
To 5-amino-2,2,4-trimethylcyclopentylmethylamine (127.72 g, 0.819 mol) in xylene (525 ml) at 122° C. was added with stirring 2,2,6-trimethyl-1,3-dioxen-4-one (232.51 g, 1.637 mol) in xylene (525 mol) over 10 minutes, during which the temperature decreased to 104° C. After heating to 113° C. over 5 minutes, vigorous effervescence and distillation of acetone (through a Vigreux column) commenced. Pot temperature was increased to 127° C. over 5 minutes and to 140° C. over a further 30 minutes, with collection of acetone distillate. After cooling to 39° C., dichloromethane was added, and removal of solvent and drying (93° C./100 Pa) gave 1-acetoacetamido-2-acetoacetamidomethyl-3,3,5-trimethylcyclopentane (237.03 g, 89%), (AAMTCP), which was crushed to a light yellow powder, mp 94-114° C. (mixture of stereoisomers), and identified by 1H-NMR, 13C-NMR, FT-IR and Raman spectra.