Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(=[O:7])[O:6][CH:4]([CH3:5])[CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[N:27]=[CH:26][CH:25]=[CH:24][C:18]=2[C:19](OCC)=[O:20])[CH:12]=[CH:13][C:14]=1[Cl:15].CC(C)([O-])C.[K+].[OH-].[K+]>>[Cl:8][C:9]1[CH:10]=[C:11]([N:16]2[C:17]3[C:18](=[CH:24][CH:25]=[CH:26][N:27]=3)[C:19]([OH:20])=[C:2]([CH2:3][CH:4]([OH:6])[CH3:5])[C:1]2=[O:7])[CH:12]=[CH:13][C:14]=1[Cl:15]
Reactant: CC1CCC(=O)O1
Reactant: CCOC(=O)c1cccnc1Nc1ccc(Cl)c(Cl)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [OH-]
Product: CC(O)Cc1c(O)c2cccnc2n(-c2ccc(Cl)c(Cl)c2)c1=O
Temperature: 110 °C
Reaction time: 5 h

Procedure:
A stirred mixture of gamma-valerolactone (40 g.), ethyl 2-(3,4-dichlorophenylamino)-nicotinate (20 g.) and potassium t-butoxide (30 g.) was warmed in an atmosphere of nitrogen to 110° C. and kept there for 5 hr. After cooling somewhat the product was poured into 1000 ml. of 5% KOH solution and was allowed to stir overnight. The basic solution was extracted with ether (2×500 ml.) and the aqueous solution was acidified to pH 5 with conc. HCl. The solid was filtered off, washed with water, dried in air then recrystallized from methanol/charcoal to yield the desired product, m.p. 232°-234° C.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH2:12])=[CH:7][CH:6]=1.[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[C:18]=1[CH:19]=O>>[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[C:18]=1[CH:19]1[N:12]([CH2:11][C:8]2[CH:7]=[CH:6][C:5]([O:4][CH2:3][C:2]([F:13])([F:14])[F:1])=[CH:10][CH:9]=2)[C:5](=[O:4])[CH2:6][CH2:7][CH2:8]1
Reactant: NCc1ccc(OCC(F)(F)F)cc1
Reactant: COc1cccc(OC)c1C=O
Product: COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc(OCC(F)(F)F)cc1

Procedure:
Prepared according to the described general procedure 6 (GP6) with commercially available (4-(2,2,2-trifluoroethoxy)phenyl)methanamine and commercially available 2,6-dimethoxybenzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions E): tR=0.80 min.; [M+H]+: 424.08 g/mol.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:14][NH:15][CH3:16]>C1COCC1>[CH3:14][N:15]([CH3:16])[S:10]([C:7]1[CH:8]=[CH:9][C:4]([C:1](=[O:3])[CH3:2])=[CH:5][CH:6]=1)(=[O:12])=[O:11]
Reactant: CNC
Reactant: CC(=O)c1ccc(S(=O)(=O)Cl)cc1
Solvent: C1CCOC1
Product: CC(=O)c1ccc(S(=O)(=O)N(C)C)cc1
Yield: 92.9 %

Procedure:
p-Acetylbenzenesulphonyl chloride (4.0 g, 18 mmol), aqueous dimethylamine (10 ml, 55 mmol), and THF (30 ml) were stirred together for 1 h at 20° C. and then partitioned between ethyl acetate and brine. The organic layer was dried (MgSO4) and evaporated under reduced pressure and the resulting residue recrystallised from either water or ether to give p-dimethylaminosulphonylacetophenone as fine white needles (3.8 g, 93%) m.p. 98°-99° C. (H2O); δH (dmso-d6) 8.0 (4H, ABq, aryl), 2.65 (9H, S, 3×Me).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([NH:21][CH2:22][C:23]3[C:24]([NH:36][CH:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[C:25]4[CH:33]=[N:32][N:31]([CH2:34][CH3:35])[C:26]4=[N:27][C:28]=3[CH2:29][CH3:30])=[O:20])[CH:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[F:8].CC1(C)C(C)(C)OB([C:51]2[CH:52]=[C:53]([CH2:57][CH:58]3[CH2:63][CH2:62][N:61](C(OC(C)(C)C)=O)[CH2:60][CH2:59]3)[CH:54]=[CH:55][CH:56]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[CH2:34]([N:31]1[C:26]2=[N:27][C:28]([CH2:29][CH3:30])=[C:23]([CH2:22][NH:21][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([C:11]([NH:10][CH2:9][C:4]4[CH:3]=[C:2]([C:55]5[CH:56]=[CH:51][CH:52]=[C:53]([CH2:57][CH:58]6[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]6)[CH:54]=5)[C:7]([F:8])=[CH:6][CH:5]=4)=[O:12])[CH:14]=3)=[O:20])[C:24]([NH:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[C:25]2[CH:33]=[N:32]1)[CH3:35]
Reactant: CC(C)(C)OC(=O)N1CCC(Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(Br)c2)c1
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+]
Solvent: C1COCCO1
Solvent: O
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(-c3cccc(CC4CCNCC4)c3)c2)c1
Reaction time: 0.5 h
Yield: 21.9 %

Procedure:
To a solution of N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (0.641 g, 0.1 mmol) in 1,4-dioxane (1.5 ml) and water (0.500 ml) was added 1,1-dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate (0.048 g, 0.120 mmol), Pd(Ph3P)4 (4.62 mg, 4.00 μmol), and K2CO3 (0.041 g, 0.300 mmol). This mixture was heated using a microwave instrument at 150° C. for 15 min. The organic layer was separated, concentrated using a Glas-Col evaporator, purified using a Gilson HPLC (with TFA), concentrated by GeneVav EZ-2 evaporator. The resulting solid was added to DCM (0.3 mL) then TFA (0.15 mL) and this mixture was left stand for 30 min before it was concentrated using a Glas-Col evaporator. The concentrate was purified using a Gilson HPLC (with TFA), concentrated by GeneVav EZ-2 evaporator, basified by amine cartridge to afford the title compound 0.016 g (21%). LC-MS m/z 732 (M+H)+.
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:8]=[C:9]([CH3:22])[CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:23]=O>>[CH:1]1([N:6]([CH3:23])[C:7]2[CH:8]=[C:9]([CH3:22])[CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(NC2CCCC2)c2[nH]c(-c3ccccn3)cc2c1
Reactant: C=O
Product: Cc1cc(N(C)C2CCCC2)c2[nH]c(-c3ccccn3)cc2c1

Procedure:
Cyclopentyl-[5-methyl-2-(pyridin-2-yl)-1H-indol-7-yl]amine prepared in Example 1 and formaldehyde were reacted according to the same procedure as Step B of Example 1 to give the title compound.
Reaction SMILES: Cl.[C:2]([OH:9])(=O)[CH2:3]/[CH:4]=[CH:5]/[CH2:6][CH3:7].[NH2:10][C@@H:11]([CH2:29][O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:13]>>[CH2:31]([O:30][CH2:29][C@H:11]([NH:10][C:2](=[O:9])[CH2:3]/[CH:4]=[CH:5]/[CH2:6][CH3:7])[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:13])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: CC/C=C/CC(=O)O
Reactant: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Agent: Cl
Product: CC/C=C/CC(=O)N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Yield: 52.5 %

Procedure:
Proceeding as in Example 1, but substituting (E)-hex-3-enoic acid hydrochloride and (S)-2-amino-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide, gave Compound 232, (S,E)-N-(3-(benzyloxy)-1-(4-(4-fluorophenoxy)phenylamino)-1-oxopropan-2-yl)hex-3-enamide (3 mg, 52.5%). MS (EI) for C28H29FN2O4. found 477.5 (MH+).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(#N)C>[CH2:15]([N:1]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: BrCc1ccccc1
Reactant: NC1CCC(O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: OC1CCC(N(Cc2ccccc2)Cc2ccccc2)CC1

Procedure:
To a mixture of 4-aminocyclohexanol (3.51 g, 23.15 mmol) and K2CO3 (12.80 g, 93 mmol) in acetonitrile (100 mL) was added benzylbromide (5.64 mL, 47.5 mmol) and the mixture was stirred at reflux for 17 hr. The crude mixture was concentrated in vacuo and the resulting residue was dissolved in water and EtOAc. The separated aqueous layer was extracted with EtOAc (2×˜100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered off and concentrated in vacuo providing crude 4-(dibenzylamino)cyclohexanol as a viscous oil, which was directly used in the next step without further purification. Yield: 6.12 g. LCMS (m/z): 296.1 [M+H]+; Retention time=0.59 min.
Reaction SMILES: [C:1]1([CH2:7][CH:8]([NH:14][C:15](=[O:33])[C:16]2[CH:21]=[CH:20][CH:19]=[N:18][C:17]=2[N:22]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:23]2)[CH:9]([OH:13])[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:34]([NH2:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[CH2:34]([NH:41][C:10](=[O:12])[CH:9]([OH:13])[CH:8]([NH:14][C:15](=[O:33])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][C:17]=1[N:22]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:23]1)[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: O=C(NC(Cc1ccccc1)C(O)C(=O)O)c1cccnc1-n1ccc(-c2ccccc2)n1
Reactant: NCc1ccccc1
Product: O=C(NC(Cc1ccccc1)C(O)C(=O)NCc1ccccc1)c1cccnc1-n1ccc(-c2ccccc2)n1

Procedure:
The reaction was carried out in analogy to reaction step 1.3 by reacting 4-phenyl-2-hydroxy-3-(2-(3-phenyl-1H-pyrazol-1-yl)nicotinamido)butanoic acid with benzylamine; ESI-MS [M+H]+: 532.2
Reaction SMILES: Cl[C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:11])[CH:9]=2)[NH:4][C:3]1=[O:12].FC(F)(F)C(O)=O.[NH2:28][C@@H:29]([CH3:35])[C:30]([N:32]([CH3:34])[CH3:33])=[O:31]>>[Cl:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[NH:4][C:3](=[O:12])[C:2]2([NH:28][C@@H:29]([CH3:35])[C:30]([N:32]([CH3:34])[CH3:33])=[O:31])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20]
Reactant: COc1ccccc1C1(Cl)C(=O)Nc2ccc(Cl)cc21
Reactant: C[C@H](N)C(=O)N(C)C
Solvent: O=C(O)C(F)(F)F
Product: COc1ccccc1C1(N[C@@H](C)C(=O)N(C)C)C(=O)Nc2ccc(Cl)cc21

Procedure:
From 4.48 g of 3,5-dichloro-3-(2-methoxyphenyl)-1,3-dihydro-2H-indol-2-one and the compound obtained in Step 61-2 (16.0 mmol, crude form) as starting materials, respectively 1.75 g (Isomer A, colorless amorphous) and 1.64 g (Isomer B, colorless powder) of two species of diastereoisomers of the title compound were obtained by a similar method to Step 4-2.
Reaction SMILES: I[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([C:14]3[S:15][C:16]([CH3:19])=[CH:17][CH:18]=3)=[O:13])=[N:7][C:6]=2[C:5]([O:20][CH3:21])=[CH:4][CH:3]=1.[N+:22]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)([O-:24])=[O:23]>>[N+:22]([C:25]1[CH:30]=[C:29]([C:2]2[C:10]3[S:9][C:8]([NH:11][C:12]([C:14]4[S:15][C:16]([CH3:19])=[CH:17][CH:18]=4)=[O:13])=[N:7][C:6]=3[C:5]([O:20][CH3:21])=[CH:4][CH:3]=2)[CH:28]=[CH:27][CH:26]=1)([O-:24])=[O:23]
Reactant: COc1ccc(I)c2sc(NC(=O)c3ccc(C)s3)nc12
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Product: COc1ccc(-c2cccc([N+](=O)[O-])c2)c2sc(NC(=O)c3ccc(C)s3)nc12
Yield: 42 %

Procedure:
5-Methyl-thiophene-2-carboxylic acid [7-(3-nitro-phenyl)-4-methoxy-benzothiazol-2-yl]-amide is synthesized from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4-methoxy-benzothiazol-2-yl)-amide (155 mg, 0.36 mmol) and 3-nitrophenylboronic acid (135 mg, 0.81 mmol) using the general procedure A as a light yellow crystalls in 42% yield. MS: m/e=425 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20](SCC)=[N:19][C:18]4=[O:25])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:28]([F:31])([F:30])[F:29])[CH:3]=1.[NH:32]1[CH2:35][CH:34]([N:36]2[CH2:41][C@H:40]([CH3:42])[O:39][C@H:38]([CH3:43])[CH2:37]2)[CH2:33]1>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:32]5[CH2:35][CH:34]([N:36]6[CH2:41][C@H:40]([CH3:42])[O:39][C@H:38]([CH3:43])[CH2:37]6)[CH2:33]5)=[N:19][C:18]4=[O:25])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:28]([F:31])([F:30])[F:29])[CH:3]=1
Reactant: CCSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1
Reactant: C[C@@H]1CN(C2CNC2)C[C@H](C)O1
Product: C[C@@H]1CN(C2CN(C3=NC(=O)C(=Cc4ccc5c(cnn5Cc5ccc(Cl)cc5C(F)(F)F)c4)S3)C2)C[C@H](C)O1

Procedure:
5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2-[3-(2,6-cis-dimethylmorpholin-4-yl)azetidin-1-yl]-1,3-thiazol-4(5H)-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 4-Azetidin-3-yl-2,6-(cis)-dimethyl-morpholine following General Procedure C.
Reaction SMILES: [CH:1]1C=CC(C([C@H]2OCC(NCCC3C=CC(F)=CC=3)C(O)C2)C2C=CC=CC=2)=CC=1.[CH2:31]([O:35][C:36]([C:38]1[N:39]=[C:40](Cl)[C:41]2[C:46]([C:47]=1[OH:48])=[CH:45][CH:44]=[C:43]([O:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]([F:59])([F:58])[F:57])=[CH:52][CH:51]=1)[CH:42]=2)=[O:37])[CH2:32][CH2:33][CH3:34]>>[CH2:31]([O:35][C:36]([C:38]1[N:39]=[C:40]([CH3:1])[C:41]2[C:46]([C:47]=1[OH:48])=[CH:45][CH:44]=[C:43]([O:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]([F:59])([F:58])[F:57])=[CH:52][CH:51]=1)[CH:42]=2)=[O:37])[CH2:32][CH2:33][CH3:34]
Reactant: OC1C[C@@H](C(c2ccccc2)c2ccccc2)OCC1NCCc1ccc(F)cc1
Reactant: CCCCOC(=O)c1nc(Cl)c2cc(Oc3ccc(C(F)(F)F)cc3)ccc2c1O
Product: CCCCOC(=O)c1nc(C)c2cc(Oc3ccc(C(F)(F)F)cc3)ccc2c1O

Procedure:
Prepared in analogy to Example D-157 d) from 4-hydroxy-1-chloro-7-(4-trifluoromethyl-phenoxy)-isoquinoline-3-carboxylic acid butyl ester (of Example D-92 f). MS-(+)-ion M+1=420.2.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[NH:17][CH:16]=[CH:15]4)[C:9](=[O:11])[NH:10][C:5]2=[N:4][CH:3]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30].C([O-])([O-])=O.[Na+].[Na+]>CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:17]1[C:18]2[C:14](=[CH:13][C:12]([N:8]3[C:6]4=[N:7][C:2]([C:25]5[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:23]([O:22][CH3:21])[CH:24]=5)=[CH:3][N:4]=[C:5]4[NH:10][C:9]3=[O:11])=[CH:20][CH:19]=2)[CH:15]=[CH:16]1
Reactant: O=c1[nH]c2ncc(Br)nc2n1-c1ccc2[nH]ccc2c1
Reactant: COc1cc(B(O)O)cc(OC)c1OC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COc1cc(-c2cnc3[nH]c(=O)n(-c4ccc5[nH]ccc5c4)c3n2)cc(OC)c1OC
Temperature: 150 °C
Yield: 19.5 %

Procedure:
To a solution of 6-bromo-1-(1H-indol-5-yl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (27 mg, 0.08 mmol) in CH3CN (1 mL) in a Personal Chemistry microwave reaction vial was added 3,4,5-trimethoxyphenylboronic acid (17 mg, 0.08 mmol), bis(triphenylphosphine)-palladium(II) dichloride (6.0 mg, 0.008 mmol), and 1 M Na2CO3 (1 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 10 min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and concentrated in vacuo. The residue was purified by preparatory HPLC to yield the title compound (6.5 mg, 19%). 1H NMR (DMSO-d6, 300 MHz): δ 12.18 (s, 1H), 11.28 (s, 1H), 8.57 (s, 1H), 7.83 (d, J=1.8 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.42 (m, 1H), 7.37 (dd, J=1.8, 8.4 Hz, 1H), 7.20 (s, 2H), 6.51 (m, 1H), 3.78 (s, 6H), 3.66 (s, 3H); HPLC retention time: 2.30 minutes; MS ESI (m/z): 418.4 (M+1)+, calc. 417.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])[CH:7]=[CH:8][CH:9]=1)([O-])=O.[H][H]>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])[CH:7]=[CH:8][CH:9]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1cccc([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1cccc(CCCN2C(=O)c3ccccc3C2=O)c1
Yield: 71.3 %

Procedure:
A solution of 190 mg (0.6 mmol) of 2-[3-(3-nitrophenyl)-propyl]-isoindole-1,3-dione in 20 ml of ethanol was treated with 50 mg of 10% palladium on charcoal and shaken in an atmosphere of hydrogen for 2 hours. The mixture was filtered and the filtrate evaporated to give 120 mg (71%) of 2-[3-(3-aminophenyl)-propyl]-isoindole-1,3-dione as a yellow oil. [Mass spectrum (ESI) MH+ =281].
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH:10]([S:29][CH2:30][C:31]([O:33]C)=[O:32])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CO>[C:1]1([CH2:7][CH2:8][CH2:9][CH:10]([S:29][CH2:30][C:31]([OH:33])=[O:32])[C:11]2[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:16]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)CSC(CCCc1ccccc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)CSC(CCCc1ccccc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Reaction time: 1 h

Procedure:
To a solution of the ester (Step III) in 20 mL of THF/MeOH (1:1) was added NaOH (6 mL, 1M). After 1 h at RT, the reaction was acidified with aqueous citric acid and the organic phase was partially evaporated. The solid was filtered off, washed with water and recrystallized from ethyl acetate/hexane to afford the title compound. m.p. 141°-143°.
Reaction SMILES: [NH2:1][C:2]1[N:11]=[CH:10][C:9]2[C:8](SC)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[NH2:14][C:15]1[CH:16]=[C:17]([OH:21])[CH:18]=[CH:19][CH:20]=1>>[NH2:1][C:2]1[N:11]=[CH:10][C:9]2[C:8]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1
Reactant: Nc1cccc(O)c1
Reactant: CSc1ncnc2cc(N)ncc12
Product: Nc1cc2ncnc(Nc3cccc(O)c3)c2cn1
Temperature: 160 °C
Reaction time: 0.25 h
Yield: 27.3 %

Procedure:
A mixture of 7-amino-4-methylthiopyrido[4,3-d]pyrimidine (299 mg, 1.56 mmole) and 3-aminophenol (1.60 g, 14.7 mmole) is stirred at 160° C. for 15 min. The resulting product is chromatographed over silica gel (9% MeOH/CH2Cl2) to give 7-amino-4-(3-hydroxyanilino)pyrido[4,3-d]pyrimidine (108 mg, 18%) as a pale orange solid. 1H NMR (DMSO) δ 9.69 (1H, brs), 9.44 (1H, brs), 9.33 (1H, s), 8.38 (1H, s), 7.37 (1H, t, J=2.1 Hz), 7.21 (1H, brd, J=8.4 Hz), 7.14 (1H, t, J=8.0 Hz), 6.59 (2H, brs), 6.53 (1H, ddd, J=7.9, 2.2, 0.8 Hz), 6.43 (1H, s).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:16]=[N:17][C:18]([NH2:21])=[N:19][CH:20]=3)=[N:13][CH:14]=2)O1.Br[C:24]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:25]=1[CH2:26][N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>>[N:27]1([CH2:26][C:25]2[CH:33]=[C:34]([C:37]([F:39])([F:38])[F:40])[CH:35]=[CH:36][C:24]=2[C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[N:19][C:18]([NH2:21])=[N:17][CH:16]=3)=[N:13][CH:14]=2)[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1
Reactant: FC(F)(F)c1ccc(Br)c(CN2CCOCC2)c1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)nc2)OC1(C)C
Product: Nc1ncc(-c2ccc(-c3ccc(C(F)(F)F)cc3CN3CCOCC3)cn2)cn1

Procedure:
The title compound was prepared in a manner similar to that described in Example 427 using 5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)pyrimidin-2-amine and 4-(2-bromo-5-(trifluoromethyl)benzyl)morpholine. MS (ESI): mass calcd. for C21H20F3N5O, 415.16; m/z found, 416.0 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.96 (s, 2H), 8.67 (dd, J=2.3, 0.9, 1H), 7.97 (dd, J=8.2, 2.3, 1H), 7.89 (dd, J=8.2, 0.9, 1H), 7.86-7.84 (m, 1H), 7.72-7.65 (m, 1H), 7.52 (d, J=7.9, 1H), 3.63-3.58 (m, 4H), 3.54-3.48 (m, 2H), 2.41-2.28 (m, 4H).
Reaction SMILES: [CH3:1][S:2]([CH2:4][S:5][CH3:6])=[O:3].[OH-].[Na+].[O:9]1[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10]1>O>[O:9]1[CH:13]=[CH:12][C:11]([CH:14]=[C:4]([S:2]([CH3:1])=[O:3])[S:5][CH3:6])=[CH:10]1
Reactant: CSCS(C)=O
Reactant: O=Cc1ccoc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CSC(=Cc1ccoc1)S(C)=O
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
To 20 ml of methyl methylsulfinylmethyl sulfide, 1.34 g (33.5 mmol) of powdered sodium hydroxide was added, followed by stirring at 80° C. for 30 minutes. This mixture was added to 9.627 g (100.2 mmol) of 3-furaldehyde, followed by stirring at 80° C. for 3 hours. After this was cooled to room temperature, water was added, followed by 3 extractions with dichloromethane. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/2) to yield 2-(3-furyl)-1-(methylsulfinyl)-1-(methylthio)ethylene.
Reaction SMILES: [OH:1][C:2]1[C:15]2[C:14](=[O:16])[CH:13]=[C:12]([C:17]([O:19]CC)=[O:18])[O:11][C:10]=2[C:9]([CH2:22][CH2:23][CH3:24])=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][CH2:7]2.C(=O)(O)[O-].[Na+].Cl>C(O)C.O>[OH:1][C:2]1[C:15]2[C:14](=[O:16])[CH:13]=[C:12]([C:17]([OH:19])=[O:18])[O:11][C:10]=2[C:9]([CH2:22][CH2:23][CH3:24])=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][CH2:7]2
Reactant: CCCc1c2c(c(O)c3c(=O)cc(C(=O)OCC)oc13)CCCC2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCCc1c2c(c(O)c3c(=O)cc(C(=O)O)oc13)CCCC2
Yield: 81.8 %

Procedure:
A refluxing solution of ethyl 6,7,8,9-tetrahydro-5-hydroxy-4-oxo-10-propyl-4H-naphtho[2,3-b]pyran-2-carboxylate (45.4 g) in ethanol (600 ml) was stirred whilst adding a solution of sodium bicarbonate (11.5 g) in water (300 ml) over 15 minutes. After refluxing a further 4 hours, an additional quantity of sodium bicarbonate solution (1.5 g in 30 ml water) was added and the mixture refluxed for a further 1 hour. The hot solution was acidified with dilute hydrochloric acid and the yellow precipitate filtered off. The damp solid was recrystallised from acetone to give 6,7,8,9-tetrahydro-5-hydroxy-4-oxo-10-propyl-4H-naphtho[2,3-b]pyran-2-carboxylic acid (34.0 g) mp 265°-268°.
Reaction SMILES: CS[C:3](=[C:9]([C:12]#[N:13])[C:10]#[N:11])[C:4]1[S:5][CH:6]=[CH:7][CH:8]=1.[C:14]1([NH:20][NH2:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[NH2:11][C:10]1[N:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:21]=[C:3]([C:4]2[S:5][CH:6]=[CH:7][CH:8]=2)[C:9]=1[C:12]#[N:13]
Reactant: NNc1ccccc1
Reactant: CSC(=C(C#N)C#N)c1cccs1
Product: N#Cc1c(-c2cccs2)nn(-c2ccccc2)c1N

Procedure:
Using 2.06 g (10 mmol) of methylthio(thiophen-2-yl)methylenepropanedinitrile and 1.1 g (10 mmol) of phenylhydrazine, the entitled product having a melting point of 165° to 167° C. was obtained in the same manner as in Example 1-(1).
Reaction SMILES: [CH3:1][C:2]([CH:6]([OH:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[CH:3][CH2:4][CH3:5].[CH:13]([O:15][CH2:16][CH3:17])=[CH2:14]>>[CH2:13]([O:15][CH:16]([O:12][CH:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[C:2]([CH3:1])=[CH:3][CH2:4][CH3:5])[CH3:17])[CH3:14]
Reactant: C=COCC
Reactant: CCC=C(C)C(O)CCCCC
Product: CCC=C(C)C(CCCCC)OC(C)OCC
Yield: 68.1 %

Procedure:
10.0 g of 4-methyl-3-decen-5-ol and 12.7 g of ethyl vinyl ether are reacted analogously to Example 9 to give 9.7 g of 5-[1'-ethoxyethoxy]-4-methyl-3-decene, boiling point 115° C./12 Torr, nD20 =1.4349, odour: green, bitterish, citrus-like, reminiscent of chocolate.
Reaction SMILES: C([O:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:23]=[C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:25]=[CH:26][CH:27]=3)[O:19][C:20]=2[CH3:21])=[C:11]([CH2:36][CH2:37][CH2:38][CH3:39])[CH:10]=1)C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[CH2:36]([C:11]1[CH:10]=[C:9]([OH:8])[CH:35]=[CH:34][C:12]=1[O:13][CH2:14][CH2:15][C:16]1[N:17]=[C:18]([C:22]2[CH:23]=[C:24]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:25]=[CH:26][CH:27]=2)[O:19][C:20]=1[CH3:21])[CH2:37][CH2:38][CH3:39]
Reactant: CCCCc1cc(OCc2ccccc2)ccc1OCCc1nc(-c2cccc(-c3ccccc3)c2)oc1C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCCCc1cc(O)ccc1OCCc1nc(-c2cccc(-c3ccccc3)c2)oc1C

Procedure:
A solution of 4-[2-(4-benzyloxy-2-butylphenoxy)ethyl]-5-methyl-2-biphenyl-3-yl-oxazole (3.16 mmol) in ethanol (100 mL) was treated with 5% Pd/C (160 mg) and hydrogen (60 psi) at ambient temperature for 18 h. The mixture was filtered and concentrated in vacuo to give 3-butyl-4-[2-(5-methyl-2-biphenyl-3-yl-oxazole-4-yl)ethoxy]phenol as a tan solid.