Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][N:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=1)[CH3:6]>C(O)(=O)C>[CH3:1][O:2][C:3](=[O:17])[CH2:4][N:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[CH:12][CH:13]=1)[CH3:6]
Reactant: COC(=O)CN(C)Cc1ccc([N+](=O)[O-])cc1
Solvent: CC(=O)O
Product: COC(=O)CN(C)Cc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.6 %

Procedure:
In acetic acid (100 ml) was dissolved N-(4-nitrobenzyl)sarcosine methyl ester (5.96 g), and to the mixture was added little by little reduced iron (7 g). The mixture was stirred at room temperature overnight. The solvent was evaporated, and to the residue was added ethyl acetate. The precipitates were filtered off, and the filtrate was washed with sodium hydroxide solution, water and saturated brine, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the resulting residue was purified with silica gel column chromatography (ethyl acetate/hexane) to give N-(4-aminobenzyl)sarcosine methyl ester (3.0 g) as red oil.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([CH3:14])=[CH:13][C:8]=2[NH:7][C:6]1=[O:15].ClCCl.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>C(N(CC)CC)C>[CH3:19][S:20]([OH:22])(=[O:1])=[O:21].[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([CH3:14])=[CH:13][C:8]=2[NH:7][C:6]1=[O:15]
Reactant: CS(=O)(=O)Cl
Agent: Cc1ccc2c(c1)[nH]c(=O)n2CCCO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)O
Reaction time: 1 h

Procedure:
To a stirred solution of 18.5 parts of 1,3-dihydro-1-(3-hydroxypropyl)-5-methyl-2H-benzimidazol-2-one in 325 parts of dichloromethane are added 11.9 parts of N,N-diethylethanamine. Then there are added dropwise (slowly) 11.5 parts of methanesulfonyl chloride. Upon completion, stirring is continued for 1 hour at reflux temperature. After cooling, the reaction mixture is washed with water, dried, filtered, and evaporated. The solid residue is crystallized from 4-methyl-2-pentanone, yielding 15 parts (58%) of 1,3-dihydro-1-(3-hydroxypropyl)-5-methyl-2H-benzimidazol-2-one methanesulfonate; mp. 125° C.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]([CH2:10][CH2:11][CH2:12][OH:13])[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>ClCCl>[CH3:23][S:24]([OH:26])(=[O:9])=[O:25].[Cl:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]([CH2:10][CH2:11][CH2:12][OH:13])[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1
Reactant: CS(=O)(=O)Cl
Agent: O=c1[nH]c2cc(Cl)ccc2n1CCCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a stirred and cooled (ice-water bath) mixture of 14.1 parts of 5-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one, 8 parts of N,N-diethylethanamine and 195 parts of dichloromethane are added dropwise 7.8 parts of methanesulfonyl chloride. Upon completion, stirring is continued first for 15 minutes while still cooling an further for 1 hour at reflux temperature. The dichloromethane is evaporated and the residue is dissolved in 4-methyl-2-pentanone and water while heating. The layers are separated and the organic phase is stirred with 100 parts of water, while cooling in an ice-bath. The precipitated product is filtered off and dried, yielding 10 parts (53%) of 5-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate; mp. 140° C.
Reaction SMILES: [I-:1].[OH:2][C:3]1[CH:4]=[C:5]([C@@H:9]([N+:11]([CH3:21])([CH3:20])[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[CH3:10])[CH:6]=[CH:7][CH:8]=1.C(#N)C.[OH-].[K+].[CH2:27]([N:29]([CH3:33])[C:30](Cl)=[O:31])[CH3:28]>C(O)CO>[I-:1].[CH2:27]([N:29]([CH3:33])[C:30]([O:2][C:3]1[CH:4]=[C:5]([C@@H:9]([N+:11]([CH3:21])([CH3:20])[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[CH3:10])[CH:6]=[CH:7][CH:8]=1)=[O:31])[CH3:28]
Reactant: CCN(C)C(=O)Cl
Reactant: C[C@@H](c1ccccc1)[N+](C)(C)[C@@H](C)c1cccc(O)c1
Agent: [I-]
Agent: [K+]
Agent: [OH-]
Solvent: CC#N
Solvent: OCCO
Product: CCN(C)C(=O)Oc1cccc([C@H](C)[N+](C)(C)[C@@H](C)c2ccccc2)c1
Temperature: 60 °C

Procedure:
Mix 7.9 g (0.02 mol) of (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 1.7 g (0.03 mol) of potassium hydroxide, 3.6 (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, heat it to 60° C. and react it for 12 hours. After it is cooled to room temperature, filter it and reduce the pressure to recover the solvent and receive 10.2 g of red-brown liquid to be directly used in the next reaction.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH2:9](Br)[CH2:10][OH:11].C([O-])([O-])=O.[K+].[K+].CC(C)=O>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: OCCOc1ccc(Br)cc1
Yield: 44.2 %

Procedure:
In a reactor, 10.0 g of 4-bromophenol, 7.95 g of ethylene bromohydrin, 16.0 g of K2CO3, and 300 ml of acetone were charged, and stirred and refluxed for 50 hours to give a reaction solution. The reaction solution was poured into water, extracted with toluene, washed with water, and thereafter dried over sodium sulfate anhydride, and the solvent was evaporated and the residue was distilled under reduced pressure in GTO (glass tube oven) to give 5.55 g (Y., 44.3%) of 1-bromo-4-(2-hydroxyethoxy) benzene.
Reaction SMILES: CC1(C)CCCC(C)(C)N1.C([Li])CCC.[Br:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23].[C:24](=[O:26])=[O:25]>C1COCC1.CCCCCC>[Br:16][C:17]1[C:18]([F:23])=[C:19]([CH:20]=[CH:21][CH:22]=1)[C:24]([OH:26])=[O:25]
Reactant: O=C=O
Reactant: Fc1ccccc1Br
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C(O)c1cccc(Br)c1F
Temperature: -10 °C
Reaction time: 1.5 h
Yield: 55 %

Procedure:
To a stirred solution of 2,2,6,6-tetramethylpiperidine (31.1 g, 0.22 mol) in THF (200 mL) was added dropwise a solution of butyl lithium (0.22 mol) in hexane (146.7 mL) at −10° C. The mixture was stirred for 1.5 h at −10° C. and the fluoroarene (1-bromo-2-fluorobenzene) in THF (100 mL) was consecutively added to the solution at −75° C. The mixture was stirred for 2 h at −75° C., before being poured on excess of CO2 gas. Then the reaction mixture was warmed to room temperature and stirred over night. After evaporation of the solvent, the residue was dissolved in water (150 mL), washed with diethyl ether (2×50 mL), acidified (to pH 1) and the solid was filtered off and dried under vacuum to give 24.3 g of the title compound as a white solid (yield: 55%).
Reaction SMILES: [CH:1]([N:14]1[CH2:17][CH:16]([OH:18])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl.C(OCC)(=O)C>[CH3:26][S:27]([O:18][CH:16]1[CH2:17][N:14]([CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:15]1)(=[O:29])=[O:28]
Reactant: OC1CN(C(c2ccccc2)c2ccccc2)C1
Reactant: CS(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.9 %

Procedure:
A mixture of 1-benzhydrylazetidin-3-ol (20.0 g, 83.68 mmol) and Et3N (12.68 g, 125.52 mmol) in DCM (200 mL) at 0° C., MsCl (11.447 mg, 100.41 mmol) was added in portions and the resulting solution was stirred at RT for 1 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the desired product (26.526 g, 100% yield).
Reaction SMILES: [BH4-].[Na+].FC(F)(F)C(O)=O.[Br:10][C:11]1[CH:12]=[CH:13][C:14]([O:29][CH3:30])=[C:15]([CH:17]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)O)[CH:16]=1.[OH-].[Na+]>C(Cl)Cl.O>[Br:10][C:11]1[CH:12]=[CH:13][C:14]([O:29][CH3:30])=[C:15]([CH:16]=1)[CH2:17][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1
Reactant: COc1ccc(Br)cc1C(O)c1cccc2ccccc12
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCl
Product: COc1ccc(Br)cc1Cc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 19 h
Yield: 95.7 %

Procedure:
3.06 g (80.89 mmol, 10.48 eq.) NaBH4 (granules) were added slowly to 50 ml Trifluoroacetic acid at 0° C. To this mixture a solution of 2.65 g (7.72 mmol) (5-Bromo-2-methoxy-phenyl)-napthalen-1-yl-methanol (62) in 30 ml dry CH2Cl2 was added which led to an brownish mixture. After stirring this mixture for 19 h at r.t. it was diluted with water and cooled again to 0° C. At this temperature NaOH-pellets were added carefully to adjust the pH to 10 before the solution was extracted with ether. The comb. org. fractions. were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 2.42 g (7.39 mmol, 95.72%) 1-(5-Bromo-2-methoxy-benzyl)-naphthalene (63) as a pale yellow oil. Rf (CH2Cl2)=0.73. 1H-NMR (400 MHz, CDCl3): δ=3.84 (s, 3H, OMe), 4.35 (s, 2H), 6.76 (d, 1H, J=8.72 Hz), 6.91 (d, 1H, J=2.53 Hz), 7.20 (dm, 1H, J1=6.82 Hz), 7.26 (dd, 1H, J1=8.84 Hz, J2=2.53 Hz), 7.38 (m, 1H), 7.41-7.49 (m, 2H), 7.74 (d, 1H, J=8.34 Hz), 7.84 (m, 1H), 7.91 (m, 1H). MS (EI): m/z=329 (18), 328 (97), 327 (20), 326 (100), 248 (16), 247 (35), 232 (22), 231 (25), 216 (20), 215 (41), 203 (17), 202 (25), 142 (21), 141 (61), 115 (10), 101 (14). HR-MS (EI): Calcd. for C18H15BrO: 326.030626. Found: 326.030567.
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]([CH3:18])=[N:16][CH:17]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH:5]=[CH:4][C:3]1=2>C1COCC1.O>[CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]([CH3:18])=[N:16][CH:17]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)nc2)=CCC3(C)C)cc1
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(C2=CCC(C)(C)c3ccc(C#Cc4ccc(C(=O)O)cc4)cc32)cn1

Procedure:
A solution of 81.7 mg (0.194 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(2-methyl-5-pyridyl)-2-naphthalenyl)ethynyl]benzoate (Compound 12) and 40.7 mg (0.969 mmol) of LiOH--H2O in 3 ml of THF/water (3:1, v/v), was stirred overnight at room temperature. The reaction was quenched by the addition of saturated aqueous NH4Cl and extracted with EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo to give the title compound as a colorless solid. 1H NMR (d6-DMSO): δ 8.41 (1H, d, J=1.9 Hz), 7.90 (2H, d, J=8.3 Hz), 7.63 (1H, dd, J=2.3, 7.9 Hz), 7.59 (2H, d, J=8.3 Hz), 7.49 (2H, m), 7.33 (1H, d, J=7.8 Hz), 6.95 (1H, s), 6.11 (1H, t, J=4.5 Hz), 2.52 (3H, s), 2.37 (2H, d, J=4.6 Hz), 1.31 (6H, s).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)CN)#[N:2].C(#N)C.[C:14](=[O:17])([O-])[OH:15].[Na+].S(OOS([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+]>[O-2].[Fe+2].O>[C:1]([C:3]1[CH:10]=[C:9]([CH:8]=[CH:5][CH:4]=1)[C:14]([OH:15])=[O:17])#[N:2]
Reactant: O=C([O-])O
Reactant: N#Cc1cccc(CN)c1
Agent: [Fe+2]
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: N#Cc1cccc(C(=O)O)c1
Temperature: 80 °C
Yield: 48.3 %

Procedure:
A mixture containing m-cyanobenzylamine (13.2 g), acetonitrile (80 g), sodium hydrogencarbonate (76 g), water (500 g), sodium persulfate (95 g), and iron oxide (0.25 g) was stirred for reaction at 80° C. over ten hours. After the precipitated solid was removed through filtration, the pH of the filtrate was adjusted to 4 through addition of sulfuric acid. The precipitated crystals were collected through filtration, washed with water, dried, to thereby obtain 7.1 g of m-cyanobenzoic acid (yield 48%, based on m-cyano-benzylamine). The m-cyanobenzoic acid obtained had a purity of 94%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[Cl:10][CH2:11][C:12](Cl)=[O:13]>C1(C)C=CC=CC=1>[Cl:10][CH2:11][C:12]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:13]
Reactant: Nc1ccccc1
Reactant: O=C(Cl)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: O=C(CCl)Nc1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Aniline (93.1 g; 1.00 mole) was dissolved in toluene (750 ml), 10 % NaOH (750 ml) was added and the stirred mixture was cooled to 0°C. Chloroacetyl chloride (197 g; 1.75 mole) was added dropwise during 45 minutes while keeping the temperature below 10°C. Stirring was continued at room temperature for about one hour. The precipitated crystalline 2-chloro-N-phenylacetamide was filtered off, washed on the filter with cold toluene and dried in vacuo at 60°C. Yield: 151 g (90.0 %); m.p. 134°-136°C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:15][CH2:16][C:17](Cl)=[O:18]>ClCCl>[C:2]1([NH:1][C:17](=[O:18])[CH2:16][Cl:15])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccccc1
Reactant: O=C(Cl)CCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(CCl)Nc1ccccc1
Temperature: 0 °C
Reaction time: 18 h
Yield: 36 %

Procedure:
A mixture of aniline (9.3 g) and triethylamine (10.1 g) in dichloromethane (40 ml) was added dropwise during 1 hour to an ice-cooled solution of chloroacetyl chloride (11.3 g) in dichloromethane (40 ml). The mixture was further stirred for 18 hours. The organic phase was separated by filtration, washed with water (3×50 ml), dried (MgSO4) and the solvent removed by evaporation to give N-phenyl-2-chloroacetamide (6.1 g) as a white solid, mp 128°-129° C., which was used without further purification.
Reaction SMILES: [NH2:1][C@@:2]1([CH2:9][C:10]#[C:11][C:12]2[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[N:13]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]>CC#N.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH3:7][N:4]1[CH2:5][CH2:6][C@:2]2([N:1]=[C:11]([C:12]3[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)[N:13]=3)[CH2:10][CH2:9]2)[C:3]1=[O:8]
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C#CC[C@]2(N)CCN(C)C2=O)n1
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CC#N
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C2=N[C@@]3(CC2)CCN(C)C3=O)n1
Reaction time: 72 h
Yield: 92.6 %

Procedure:
Silver trifluoromethanesulphonate (358.56 mg, 1.4 mmol) was added to a solution of (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (2.71 g, 6.98 mmol) (which may be prepared as described in Description 8) in MeCN (60 mL) at 50° C. and the reaction was stirred for 3 days. Additional AgOTf (10 mol %) was added and stirring was continued for 24 hrs. The solvent was evaporated and the residue was suspended in EtOAc. The organics were washed with water, dried (Na2SO4) and the solvent evaporated to afford a light brown oil. This was purified using a Biotage Isolera with a 100 g SNAP cartridge, eluting with 0 to 100% (mixture of 1% of 2M NH3 in MeOH; 9% MeOH; 90% EtOAc) in EtOAc, affording the (55)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D9) (2.51 g, 6.4626 mmol, 92.6% yield) as a light brown solid;
Reaction SMILES: [CH:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10]O)[CH2:5][CH2:4]1)=[O:2].[SH:12][C:13]1[NH:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[N:17]=1.C(N(CC)C(C)C)(C)C.[I-].C(C[P+](C)(C)C)#N>C(#N)CC.O>[CH:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][S:12][C:13]2[NH:14][C:15]3[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:5][CH2:4]1)=[O:2]
Reactant: Sc1nc2ccccc2[nH]1
Reactant: O=CN1CCN(CCO)CC1
Agent: C[P+](C)(C)CC#N
Agent: [I-]
Solvent: CCC#N
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=CN1CCN(CCSc2nc3ccccc3[nH]2)CC1
Yield: 86.1 %

Procedure:
To a solution containing 1-formyl-4-(2-hydroxyethyl)piperazine (1.90 g, 12 mmol), 2-mercaptobenzimidazole (1.50 g, 10 mmol), and N,N-diisopropylethylamine (1.80 g, 14 mmol) in propionitrile (16 mL), cyanomethyltrimethylphosphonium iodide (2.80 g, 11.5 mmol) was added under argon, and the mixture was refluxed for 2 hours. After cooling, the reaction mixture was poured into water (100 mL), and the liquid was subjected to extraction with chloroform (100 mL×3) . The organic layer was washed with saturated brine, followed by drying over sodium sulfate anhydrate and removing the solvent through filtration. The thus-formed crude product was crystallized from acetone-diethyl ether, thereby yielding 2.50 g of 1-formyl-4-[2-(benzimidazol-2-ylthio)ethyl]piperazine (yield: 86%) as a colorless crystalline powder.
Reaction SMILES: [CH:1]1[N:5]=[CH:4][N:3]2[CH:6]([C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=3/[CH:17]=[CH:18]/[CH3:19])[CH2:7][CH2:8][C:2]=12>[Pd].CCO>[CH:1]1[N:5]=[CH:4][N:3]2[CH:6]([C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=3[CH2:17][CH2:18][CH3:19])[CH2:7][CH2:8][C:2]=12
Reactant: C/C=C/c1cc(C#N)ccc1C1CCc2cncn21
Agent: [Pd]
Solvent: CCO
Product: CCCc1cc(C#N)ccc1C1CCc2cncn21

Procedure:
A suspension of 4-(6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-((E)-propenyl)benzonitrile (0.150 g, 0.602 mmol), 20% (w/w) palladium on carbon (0.040 g), THE (15 mL), and EtOH (15 mL) is stirred under an atmosphere of hydrogen (1 atm) for 60 h. The suspension is the filtered and the filtrate concentrated. The residue is then purified by flash chromatography (Hexane/EtOAc, and then 10% MeOH/EtOAc) to give 4-(6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-(n-propyl)benzonitrile as a white solid. MS (ESI) m/z 252.1 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.04 (t, J=7.3 Hz, 3H), 1.63-1.77 (m, 2H), 2.33-2.45 (m, 1H), 2.62-2.80 (m, 2H), 2.92 (app t, J=7.1 Hz, 2H), 3.04-3.19 (m, 1H), 5.58 (dd, J=7.8, 5.6 Hz, 1H), 6.73 (d, J=8.1 Hz, 1H), 6.81 (s, 1H), 7.25 (s, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.51 (s, 1H).
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])(=O)=O.[Br-:24].[Mg+2].[Br-]>CCOCC>[CH2:6]([Br:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOS(C)(=O)=O
Reactant: [Br-]
Agent: [Mg+2]
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\CCCCCCCCBr
Temperature: 25 °C
Reaction time: 24 h
Yield: 97.3 %

Procedure:
Linoleyl methanesulfonate (27 g, 78 mmoles), anhydrous magnesium bromide (43 g; 238 mmoles), and 1000 ml of dry ether was placed in a 2500 ml three-necked flask equipped with reflux condenser, inlet and outlet tubes for dry nitrogen, and mechanical stirrer. The mixture was stirred vigorously at room temperature for 24 hr. More ether, and cold, degassed water were added after 24 hours. The water layer was extracted twice with ether. The combined ether phases were washed consecutively with water, 1% potassium carbonate solution, and water, and are dried over anhydrous sodium sulfate. Concentration of the ether phase using a rotary evaporator yielded 25 g (97%) of linoleyl bromide; mp −35° C.
Reaction SMILES: [CH:1]1[C:6](Cl)=[CH:5][C:4]2[C:8]([C:10]3[C:15]([NH:16][C:3]=2[CH:2]=1)=[CH:14][C:13]1[C:17]([C:19]2[CH:25]=[C:24](Cl)[CH:23]=[CH:22][C:20]=2[NH:21][C:12]=1[CH:11]=3)=[O:18])=[O:9].COC1C=CC(NC2C=C(C(O)=O)C(NC3C=CC(OC)=CC=3)=CC=2C(O)=O)=CC=1.P(=O)(O)(O)O.CO>O>[CH:24]1[CH:25]=[C:19]2[C:17]([C:13]3[C:12]([NH:21][C:20]2=[CH:22][CH:23]=1)=[CH:11][C:10]1[C:8]([C:4]2[C:3]([NH:16][C:15]=1[CH:14]=3)=[CH:2][CH:1]=[CH:6][CH:5]=2)=[O:9])=[O:18]
Reactant: O=c1c2cc(Cl)ccc2[nH]c2cc3c(=O)c4cc(Cl)ccc4[nH]c3cc12
Agent: COc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(OC)cc3)cc2C(=O)O)cc1
Agent: O=P(O)(O)O
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 113 °C
Reaction time: 0.5 h
Yield: 434 %

Procedure:
To 270 g of polyphosphoric acid (117% phosphoric acid) heated at 85° C. was added 0.54 g of N-[3-(N,N-dimethylaminopropyl)] copper phthalocyanine followed by 13.5 g of 2,9-dichloroquinacridone. The mixture was stirred at 113° C. for 30 minutes, after which 40.5 g of 2,5-di(4-methoxyanilino)terephthalic acid was added. The resultant mixture was heated at 113° C. for five hours. After the melt was cooled to 95° C., the acid strength was adjusted to 113% by the dropwise addition of phosphoric acid. The mixture was slowly poured into 470 g methanol. The slurry was heated at reflux for two hours, diluted with water, and stirred at 60° C. for thirty minutes. The slurry was further diluted with water, after which the solid component was collected by filtration and washed with water until acid free. The presscake was reslurried in water (320 g total water), the pH adjusted to 8.5 with dilute aqueous sodium hydroxide, and 320 g of methanol was added. The resultant slurry was heated at 120° C. for six hours in a closed system (e.g., a pressure reactor). After the slurry was cooled to 45°-50° C., 4.8 g of wood rosin (as the sodium salt) was added. After the mixture was stirred for 30 minutes, 10.0 g of CaCl2.2H2O (dissolved in water) was added, the slurry stirred for one hour, and the pH acidified (if necessary) with phosphoric acid. The solid component was collected by filtration and washed with water. The wet cake can be dried or used as is for specific applications. Here, the wet cake was oven dried at 60° C. to give approximately 48 g of quinacridone as a deep violet pigment.
Reaction SMILES: [O:1]=[C:2]1[C:11]2([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH2:10][C:9]2[C:4](=[N:5][CH:6]=[C:7](/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:8]=2)[NH:3]1.[C:24](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O>ClCCCl>[CH3:24][N:14]1[CH2:13][CH2:12][C:11]2([CH2:10][C:9]3[C:4](=[N:5][CH:6]=[C:7](/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:8]=3)[NH:3][C:2]2=[O:1])[CH2:16][CH2:15]1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: CCOC(=O)/C=C/c1cnc2c(c1)CC1(CCNCC1)C(=O)N2
Agent: C=O
Agent: [Na+]
Solvent: ClCCCl
Product: CCOC(=O)/C=C/c1cnc2c(c1)CC1(CCN(C)CC1)C(=O)N2
Temperature: 70 °C

Procedure:
To a suspension of (E)-ethyl 3-(2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-6-yl)acrylate (99.8 mg, 0.316 mmol) in 1,2-dichloroethane (5 mL) were added sodium triacetoxyborohydride (139 mg, 0.656 mmol) and paraformaldehyde (21 mg, 0.699 mmol). The reaction mixture was heated to 70° C. for 5 h. After cooling to room temperature, the reaction mixture was partitioned between DCM (25 mL) and water (25 mL). The aqueous layer was separated and extracted with DCM (2×20 mL). The combined organic phases were washed with saturated NaHCO3 (3×25 mL) and brine (25 mL), dried over sodium sulfate and concentrated. The crude product was used directly in the next step.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:7]=1
Reactant: O=c1ccc(Br)c[nH]1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1cc(Br)ccc1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 57.7 %

Procedure:
To a solution of compound 5-bromopyridin-2(1H)-one (348 mg, 2.0 mmol) and K2CO3 (830 mg, 6.0 mmol) in DMF (15 mL) was added ethyl bromoacetate dropwise. The mixture was stirred at room temperature for 2 h, filtered, and the filtrate was concentrated in vacuo. The residue was purified by prep TLC (1:1 PE/EtOAc) to afford ethyl 2-(5-bromo-2-oxopyridin-1(2H)-yl)acetate (300 mg, 57.7%). 1H NMR CDCl3: δ 7.41-7.26 (m, 2H), 6.53-6.5 (d, 1H), 4.59 (s, 2H), 4.28-4.21 (q, 2H), 1.32-1.23 (q, 3H).