Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:44])[C@@H:4]([NH:14][C:15]([C:17]1[N:18]=[C:19]([CH2:38][CH:39]2[CH2:43][CH2:42][CH2:41][CH2:40]2)[C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[C:22]([O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=1)[CH:21]=2)=[O:16])[CH2:5][C:6]1[S:7][C:8]([C:11]([CH3:13])=[CH2:12])=[CH:9][CH:10]=1>[Pd]>[C:34]([C:31]1[CH:30]=[CH:29][C:28]([O:27][C:22]2[CH:21]=[C:20]3[C:25]([CH:26]=[C:17]([C:15]([NH:14][C@@H:4]([CH2:5][C:6]4[S:7][C:8]([CH:11]([CH3:12])[CH3:13])=[CH:9][CH:10]=4)[C:3]([OH:44])=[O:2])=[O:16])[N:18]=[C:19]3[CH2:38][CH:39]3[CH2:40][CH2:41][CH2:42][CH2:43]3)=[CH:24][CH:23]=2)=[CH:33][CH:32]=1)([CH3:36])([CH3:35])[CH3:37]
Reactant: C=C(C)c1ccc(C[C@H](NC(=O)c2cc3ccc(Oc4ccc(C(C)(C)C)cc4)cc3c(CC3CCCC3)n2)C(=O)OC)s1
Agent: [Pd]
Product: CC(C)c1ccc(C[C@H](NC(=O)c2cc3ccc(Oc4ccc(C(C)(C)C)cc4)cc3c(CC3CCCC3)n2)C(=O)O)s1

Procedure:
The title compound was prepared by the treatment of 2(S)-{[7-(4-tert-Butyl-phenoxy)-1-cyclopentylmethyl-isoquinoline-3-carbonyl]-amino}-3-(5-isopropenylthiophen-2-yl)-propionic acid methyl ester (prepared in Example 29) with Pd/C and H2 gas (1 atm) by the general procedure N to afford 2(S)-{[7-(4-tert-Butyl-phenoxy)-1-cyclopentylmethyl-1-isoquinoline-3-carbonyl]-amino}-3-(5-isopropylthiophen-2-yl)-propionic acid methyl ester. This ester was hydrolyzed by the general procedure C to afford the title compound.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH2:8][S:7][C@@H:6]1Br)(=[O:3])[CH3:2].[SH:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1>C1(C)C=CC=CC=1.C(#N)C.[O-2].[Zn+2]>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH2:8][S:7][C@H:6]1[S:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1)(=[O:3])[CH3:2]
Reactant: N#Cc1ccc(S)cc1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@@H](Br)SC[C@H]1OC(C)=O
Agent: [O-2]
Agent: [Zn+2]
Solvent: CC#N
Solvent: Cc1ccccc1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](Sc2ccc(C#N)cc2)SC[C@H]1OC(C)=O
Temperature: 50 °C
Reaction time: 18 h
Yield: 64 %

Procedure:
A suspension of 16.9 g (47.10-3 mol) of 2,3,4-tri-O-acetyl-5-thio-α-D-xylopyranosyl bromide, 6 g (43.10-3 mol) of 4-mercaptobenzonitrile and 3.5 g (43.10-3 mol) of zinc oxide (ZnO) in 120 ml of anhydrous toluene and 120 ml of acetonitrile is stirred under an inert atmosphere, in the presence of a molecular sieve (1 mm), for 18 hours, at 50° C. After the reaction medium has been filtered on Celite® in ethyl acetate, the organic phase obtained is washed with a 1N solution of HCl twice, a 1N solution of sodium hydroxide and finally water, dried over magnesium sulfate and evaporated under reduced pressure. After precipitation in ether, 11.30 g (yield: 64%) of the expected product are obtained.
Reaction SMILES: [CH2:1]([O:4][N:5]=[C:6]([C:12]1[N:13]=[C:14]([NH2:17])[S:15][CH:16]=1)[C:7]([O:9]CC)=[O:8])[CH2:2][CH3:3].CO.[OH-].[Na+]>O1CCCC1>[CH2:1]([O:4][N:5]=[C:6]([C:12]1[N:13]=[C:14]([NH2:17])[S:15][CH:16]=1)[C:7]([OH:9])=[O:8])[CH2:2][CH3:3]
Reactant: CCCON=C(C(=O)OCC)c1csc(N)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCCON=C(C(=O)O)c1csc(N)n1
Reaction time: 5 h
Yield: 69.6 %

Procedure:
A solution of ethyl 2-n-propoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetate (syn isomer) (10 g.) in a mixture of tetrahydrofuran (39 ml.), methanol (39 ml.) and 1 N sodium hydroxide (75.8 ml.) was stirred at 35° to 40° C. for 5 hours. After the resultant solution was concentrated under reduced pressure, the aqueous residue was adjusted to pH 2.5 with 10% hydrochloric acid. The precipitates were collected by filtration and dried to give 2-n-propoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid (syn isomer) (6.2 g.), mp. 161° C. (dec.).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([N+:20]([O-])=O)=[C:5]([C:9]2[O:10][C:11]3[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=3[C:13](=[O:15])[CH:14]=2)[CH:6]=[CH:7][CH:8]=1>CO.C1COCC1.[Ni]>[NH2:20][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[C:9]1[O:10][C:11]2[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13](=[O:15])[CH:14]=1
Reactant: COc1cccc(-c2cc(=O)c3ccccc3o2)c1[N+](=O)[O-]
Agent: [Ni]
Solvent: C1CCOC1
Solvent: CO
Product: COc1cccc(-c2cc(=O)c3ccccc3o2)c1N
Yield: 58.1 %

Procedure:
2-(3-Methoxy-2-nitrophenyl)-4-oxo-4H-[1]benzopyran (1.73 g, 5.8 mmol) in methanol (50 mL) and THF (50 mL) is hydrogenated under pressure with RaNi (0.5 g). The solution is concentrated under reduced pressure and recrystallized from toluene to yield 2-(2-amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran (900 mg, 58%) as a solid. 1H NMR (DMSO): δ8.07 (1H, d, J=8.0 Hz), 7.83 (1H, t, J=6.9 Hz), 7.70 (1H, d, J=7.7 Hz), 7.51 (1H, t, J=7.0 Hz), 7.09 (1H, d, J=8.0 Hz), 7.00 (1H, d, J=7.0 Hz), 6.71 (1H, t, J=8.0 Hz), 6.56 (1H, s), 5.30 (2H, s), 3.85 (3H, s).
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[NH:10][NH:9][C:8]2=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].[N+]([O-])=O>C(Cl)Cl>[C:1]1([N:7]2[C:8](=[O:13])[N:9]=[N:10][C:11]2=[O:12])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=c1[nH][nH]c(=O)n1-c1ccccc1
Agent: O=S(=O)([O-])[O-]
Agent: O=[N+][O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=C1N=NC(=O)N1c1ccccc1

Procedure:
4-Phenylurazole (25gm) and anhydrous sodium sulphate were suspended in methylene chloride. The suspension was cooled in ice and nitrogen dioxide was passed in until all the 4-phenylurazole dissolved. The solution was filtered and the solvent removed under reduced pressure. The solid was either used as obtained or purified by sublimation (at 100°C and 10-5 mm of mercury).
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([O:14][C:15]2[N:20]=[C:19]3[S:21][C:22]([NH2:24])=[N:23][C:18]3=[CH:17][CH:16]=2)[CH:11]=[CH:10][C:9]=1[F:25])([CH3:4])([CH3:3])[CH3:2].[C:27](Cl)(=[O:29])[CH3:28].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([O:14][C:15]2[N:20]=[C:19]3[S:21][C:22]([NH:24][C:27](=[O:29])[CH3:28])=[N:23][C:18]3=[CH:17][CH:16]=2)[CH:11]=[CH:10][C:9]=1[F:25])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1cc(Oc2ccc3nc(N)sc3n2)ccc1F
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)Nc1nc2ccc(Oc3ccc(F)c(NC(=O)OC(C)(C)C)c3)nc2s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.8 %

Procedure:
To a solution of tert-butyl{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-fluorophenyl}carbamate (1.13 g, 3.0 mmol) produced in Example C63(iv) and N,N-dimethylpyridine-4-amine (1.22 g, 10 mmol) in pyridine (10 mL) was added dropwise acetyl chloride (0.79 g, 10 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water (200 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0), and triturated with diethyl ether to give the title compound (0.65 g, 52%) as a white amorphous.
Reaction SMILES: Br[C:2]1[N:3]([CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.C([O-])([O-])=O.[Na+].[Na+].[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O1CCOCC1.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>[C:25]([O:24][C:22](=[O:23])[CH2:21][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2)[C:10]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:2]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([CH3:28])([CH3:27])[CH3:26]
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(Br)n(CC(=O)OC(C)(C)C)c2c1
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3)n(CC(=O)OC(C)(C)C)c2c1
Temperature: 80 °C
Yield: 88 %

Procedure:
To a solution of methyl 2-bromo-1-(2-tert-butoxy-2-oxoethyl)-3-cyclohexyl-1H-indole-6-carboxylate in dioxane (0.06 M) was added bis(triphenylphosphine)palladium(II) dichloride (0.2 eq) at RT under a nitrogen atmosphere. Then aqueous Na2CO3 (2 M; 4 eq) followed by phenylboronic acid (2.5 eq) were added and the reaction was heated to 80° C. for 2 h. The reaction mixture was allowed to cool and concentrated in vacuo. DCM was added and the organic phase washed with H2O, brine and dried over Na2SO4 before being filtered and concentrated in vacuo. The crude material was purified by automated FC (SiO2; 95:5 EtOAc/PE) to afford the title compound (88%). (ES+) m/z 448 (M+H)+
Reaction SMILES: [C:1]([S:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:16]=O)[CH:14]=2)[N:9]=[CH:8][C:7]=1[C:18]#[N:19])([CH3:4])([CH3:3])[CH3:2].COC1C=CC(/C=[C:35]2/[C:36]([NH:38][C:39]([S:41]/2)=[NH:40])=[O:37])=CC=1OC1CCCC1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[NH2:40][C:39]1[S:41]/[C:35](=[CH:16]\[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[CH:8][C:7]([C:18]#[N:19])=[C:6]3[S:5][C:1]([CH3:4])([CH3:3])[CH3:2])/[C:36](=[O:37])[N:38]=1
Reactant: COc1ccc(/C=C2\SC(=N)NC2=O)cc1OC1CCCC1
Reactant: CC(C)(C)Sc1c(C#N)cnc2ccc(C=O)cc12
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(C)Sc1c(C#N)cnc2ccc(/C=C3\SC(N)=NC3=O)cc12

Procedure:
Similar procedure as described in example 38 was used, starting from 4-tert-butylsulfanyl-6-formyl-quinoline-3-carbonitrile (example 39b), pseudothiohydantoin, sodium acetate and acetic acid to give 6-[2-amino-4-oxo-4H-thiazol-(5Z)-ylidenemethyl]-4-tert-butylsulfanyl-quinoline-3-carbonitrile. LC-MS m/e 369 (MH+).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:12]=[CH:11][C:10]2=[O:23])=[CH:4][CH:3]=1.C[Si](Cl)(C)C.[Na+].[I-:30]>C(#N)CC>[I:30][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:12]=[CH:11][C:10]2=[O:23])=[CH:4][CH:3]=1
Reactant: COc1ccc(-c2ccc(=O)n(Cc3ccc(Cl)nc3)c2)cc1
Reactant: [I-]
Agent: C[Si](C)(C)Cl
Agent: [Na+]
Solvent: CCC#N
Product: COc1ccc(-c2ccc(=O)n(Cc3ccc(I)nc3)c2)cc1

Procedure:
According to Scheme 33 Step 1: 1-((6-Chloropyridin-3-yl)methyl)-5-(4-methoxyphenyl)pyridin-2(1H)-one (2.54 mmol, 0.83 g), trimethylsilyl chloride (3.3 mmol, 0.42 mL) and NaI (7.60 mmol, 1.14 g) in propionitrile (20 mL) were heated at 140° C. for 20 minutes under microwave irradiation conditions. Then the suspension was filtered off and the solid obtained was partitioned between CH2Cl2/water. The aqueous layer was extracted several times with CH2Cl2; the organic layers were combined, dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was treated with Et2O giving an 1-((6-iodopyridin-3-yl)methyl)-5-(4-methoxyphenyl)pyridin-2(1H)-one (600 mg, 61%) as a pale grey solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:15][CH3:16])=[N:4][C:5]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:7]=1.[C:17]([OH:21])(=O)[CH2:18]O>>[OH:21][CH2:17][C:18]1[N:15]([CH3:16])[C:3]2=[N:4][C:5]([S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:6][CH:7]=[C:2]2[N:1]=1
Reactant: CNc1nc(Sc2ccccc2)ccc1N
Reactant: O=C(O)CO
Product: Cn1c(CO)nc2ccc(Sc3ccccc3)nc21

Procedure:
A procedure similar to that described in Preparation 43 was repeated, except that 2.62. g of 3-amino-2-methylamino-6-phenylthiopyridine (prepared as described in Preparation 89) and 2.58 g of glycolic acid were used, and that the product was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of ethyl acetate and methanol in ratios ranging from 50:1 to 10:1 by volume as the eluent, to give 1.80 g of the title compound, melting at 119-120° C.
Reaction SMILES: C([O:3][C:4]([CH2:6][CH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH:18]2[O:22][CH2:21][CH2:20][O:19]2)=[CH:10][CH:9]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>C1COCC1.O>[OH:3][CH2:4][CH2:6][CH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH:18]2[O:19][CH2:20][CH2:21][O:22]2)=[CH:10][CH:9]=1
Reactant: CCOC(=O)CCc1ccc(C2OCCO2)c2ccccc12
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: OCCCc1ccc(C2OCCO2)c2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 37.1 %

Procedure:
To a solution of 2-[4-(2-ethoxycarbonylethyl)naphthyl]dioxolane (210 mg, 0.70 mmol) in anhydrous THF (5 mL) was added at 0° C. 1M lithium aluminum hydride in THF (0.5 mL). THF (5 mL) was added and the mixture was stirred at room temperature for 16 hr, diluted with water (10 mL), acidified with conc. hydrochloric acid, and extracted with ether (3×10 mL). The combined organic extracts were dried (MgSO4), and concentrated. The residue was purified by flash chromatography using hexane/ethyl acetate 2:1 as eluent to provide 67 mg (37%) of a colorless oil.
Reaction SMILES: Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[C:25](=[O:26])[C:14]3[CH:15]=[N:16][C:17]4[C:18]([O:23][CH3:24])=[CH:19][CH:20]=[CH:21][C:22]=4[C:13]=3[N:12]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[C:11]2=[O:33])[CH:7]=[CH:8][CH:9]=1.[CH2:34]([S:36](Cl)(=[O:38])=[O:37])[CH3:35]>>[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[C:25](=[O:26])[C:14]3[CH:15]=[N:16][C:17]4[C:18]([O:23][CH3:24])=[CH:19][CH:20]=[CH:21][C:22]=4[C:13]=3[N:12]([CH:27]3[CH2:32][CH2:31][N:30]([S:36]([CH2:34][CH3:35])(=[O:38])=[O:37])[CH2:29][CH2:28]3)[C:11]2=[O:33])[CH:7]=[CH:8][CH:9]=1
Reactant: CCS(=O)(=O)Cl
Reactant: COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n(C3CCNCC3)c12
Agent: Cl
Product: CCS(=O)(=O)N1CCC(n2c(=O)n(-c3cccc(Cl)c3)c(=O)c3cnc4c(OC)cccc4c32)CC1

Procedure:
3-(3-Chloro-phenyl)-1-(1-ethanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione (32 mg) was prepared according to general procedure H from 3-(3-chloro-phenyl)-7-methoxy-1-piperidin-4-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione.dihydrochloride (40 mg) and ethanesulfonyl chloride. LCMS: m/z 529 [M+1]+.
Reaction SMILES: C[O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[NH:12][C:13]1[C:22]([NH:23][S:24]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)(=[O:26])=[O:25])=[N:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1.C([O-])([O-])=O.[K+].[K+].O>CO>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:33])=[O:2])=[C:5]([NH:12][C:13]2[C:22]([NH:23][S:24]([C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)(=[O:25])=[O:26])=[N:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)[CH:6]=1
Reactant: COC(=O)c1ccc(OC)cc1Nc1nc2ccccc2nc1NS(=O)(=O)c1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1ccc(C(=O)O)c(Nc2nc3ccccc3nc2NS(=O)(=O)c2cccnc2)c1
Reaction time: 1 h
Yield: 94.1 %

Procedure:
Methyl-4-methoxy-2-({3-[(pyridin-3-ylsulfonyl)amino]quinoxalin-2-yl}amino)benzoate (2200 mg; 4.73 mmol; 1 eq) and K2CO3 (8.5 g; 61.44 mmol; 13 eq) are taken up in MeOH (100 mL) and water (25 mL) and heated up to 60° C. overnight. The reaction mixture is concentrated to half the volume and some black residue is removed by filtration. The clear solution is neutralised with aqueous citric acid 10%. After 1 h at 4° C., the precipitate formed is filtered off and washed with water. After drying under vacuum at 40° C. overnight, it affords 2.01 g (94%) of the title compound as a yellow powder. 1H NMR (DMSO-d6) δ 13.17 (s, 1H), 12.49 (br s, 1H), 12.27 (s, 1H), 9.25 (d, J=1.9 Hz, 1H), 9.08 (d, J=2.6 Hz, 1H), 8.81-8.79 (m, 1H), 8.47-8.43 (m, 1H), 7.98 (d, J=9.0 Hz, 1H), 7.93 (br s, 1H), 7.68-7.60 (m, 2H), 7.44-7.40 (m, 2H), 6.70 (dd, J=8.7, 2.6 Hz, 1H), 3.91 (s, 3H). HPLC (max plot) 99%; Rt 4.04 min. LC/MS: (ES+): 452.3, (ES−): 450.3.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[C:31]4[C:30]5[CH:29]=[CH:28][C:27]([O:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:26][C:25]=5[NH:24][C:23]=4[C:22]([C:37]([O:39][CH3:40])=[O:38])=[N:21][N:20]=3)[C:14]=2[CH3:41])=[C:6]([CH:10]=1)[C:7](O)=[O:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[C:6]2[C:5]([CH2:11][N:12]([C:13]3[C:14]([CH3:41])=[C:15]([C:19]4[C:31]5[C:30]6[CH:29]=[CH:28][C:27]([O:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:26][C:25]=6[NH:24][C:23]=5[C:22]([C:37]([O:39][CH3:40])=[O:38])=[N:21][N:20]=4)[CH:16]=[CH:17][CH:18]=3)[C:7]2=[O:8])=[CH:4][CH:3]=1
Reactant: COCCOc1ccc2c(c1)[nH]c1c(C(=O)OC)nnc(-c3cccc(NCc4ccc(Cl)cc4C(=O)O)c3C)c12
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COCCOc1ccc2c(c1)[nH]c1c(C(=O)OC)nnc(-c3cccc(N4Cc5ccc(Cl)cc5C4=O)c3C)c12
Temperature: 25 °C
Reaction time: 6 h
Yield: 17.5 %

Procedure:
A solution of 5-chloro-2-((3-(4-(methoxycarbonyl)-7-(2-methoxyethoxy)-5H-pyridazino [4,5-b]indol-1-yl)-2-methylphenylamino)methyl)benzoic acid (0.227 g, 0.394 mmol), BOP (0.366 g, 0.827 mmol), and N-methylmorpholine (0.273 mL, 2.482 mmol) in DMF (3.94 mL) under nitrogen was heated at 45° C. After 6 hr, the reaction was cooled to room temperature, dissolved in EtOAc (100 mL) and washed with water (3×25 mL) and brine (25 mL), dried over MgSO4, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 24 g column eluting with 0-5% MeOH/CH2Cl2. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.0384 g, 0.069 mmol, 17.5% yield) as a light orange solid.
Reaction SMILES: C#C.[CH:3]([Si:5]([N:12]([CH3:14])[CH3:13])([N:9]([CH3:11])[CH3:10])[N:6]([CH3:8])[CH3:7])=[CH2:4]>>[CH2:3]([Si:5]([N:9]([CH3:10])[CH3:11])([N:6]([CH3:8])[CH3:7])[N:12]([CH3:13])[CH3:14])[CH3:4]
Reactant: C=C[Si](N(C)C)(N(C)C)N(C)C
Agent: C#C
Product: CC[Si](N(C)C)(N(C)C)N(C)C
Temperature: 240 °C
Yield: 85 %

Procedure:
The reaction was carried out as in Example 3; however, the acetylene pressure was increased to 150 psig and the reaction temperature was maintained at 240° C. Vinyltris(dimethylamino)silane was the single major product at a yield of 85% theoretical. Ethyltris(dimethylamino)silane and 1,2-bis(trisdimethylamino)silylethane were also formed, each in approximately a 2 to 3% yield. Vinyltris(dimethylamino)silane was also formed in approximately 10% yield.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:31][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[O:21][CH:22]([CH3:30])[C:23]([O:25]C(C)(C)C)=[O:24])[C:7]=2[C:6]=1[CH3:32])=[O:4].FC(F)(F)C(O)=O>ClCCl>[F:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:12]2[C:7]3[C:6]([CH3:32])=[C:5]([C:3]([O:2][CH3:1])=[O:4])[S:31][C:8]=3[N:9]=[CH:10][N:11]=2)=[C:15]([CH:16]=1)[O:21][CH:22]([CH3:30])[C:23]([OH:25])=[O:24]
Reactant: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3OC(C)C(=O)OC(C)(C)C)c2c1C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3OC(C)C(=O)O)c2c1C

Procedure:
Prepared analogously to example 8.1 using methyl-4-(2-(1-tert-butoxy-1-oxopropan-2-yloxy)-4-fluorophenylamino)-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylate (2.1 g) and 50% trifluoroacetic acid in dichloromethane (20 ml).
Reaction SMILES: [Cl:1][C:2]1[C:10]([NH2:11])=[C:6]2[CH2:7][CH2:8][O:9][C:5]2=[CH:4][CH:3]=1.[Br:12]N1C(=O)CCC1=O>C1C=CC=CC=1>[Br:12][C:4]1[CH:3]=[C:2]([Cl:1])[C:10]([NH2:11])=[C:6]2[C:5]=1[O:9][CH2:8][CH2:7]2
Reactant: Nc1c(Cl)ccc2c1CCO2
Reactant: O=C1CCC(=O)N1Br
Solvent: c1ccccc1
Product: Nc1c(Cl)cc(Br)c2c1CCO2
Yield: 87.9 %

Procedure:
A solution of 9.1 parts of 5-chloro-2,3-dihydro-4-benzofuranamine [described in J. Het. Chem., 17(6) 1333 (1980)], 9.6 parts of N-bromosuccinimide and 130.5 parts of benzene was stirred for 1 hour at reflux temperature. The solvent was evaporated and the residue was dissolved in 387.4 parts of trichloromethane. The solution was washed with water (2×200 parts). The organic layer was dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; C6H14 /CH2Cl2 50:50). The eluent of the desired fraction was evaporated, yielding 11.8 parts (87.9%) of 7-bromo-5-chloro-2,3-dihydro-4-benzofuranamine (interm. 8).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([C:14]([OH:16])=O)=[CH:12][O:11][N:10]=2)=[CH:5][CH:4]=1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.Cl.[CH3:50][C:51]1[N:56]=[CH:55][C:54]([C:57]2([OH:62])[CH2:61][CH2:60][NH:59][CH2:58]2)=[CH:53][CH:52]=1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:13]([C:14]([N:59]3[CH2:60][CH2:61][C:57]([C:54]4[CH:55]=[N:56][C:51]([CH3:50])=[CH:52][CH:53]=4)([OH:62])[CH2:58]3)=[O:16])=[CH:12][O:11][N:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2nocc2C(=O)O)cc1
Reactant: Cc1ccc(C2(O)CCNC2)cn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(-c2nocc2C(=O)N2CCC(O)(c3ccc(C)nc3)C2)cc1
Yield: 26.4 %

Procedure:
A solution of 3-(4-methoxyphenyl)isoxazole-4-carboxylic acid (7 mg, 0.03 mmol), N-ethyl-N-isopropylpropan-2-amine (16 μL, 0.09 mmol, 3 equ.) and TBTU (12 mg, 0.036 mmol, 1.2 equ.) in DMF (0.3 mL) was added to 3-(6-methylpyridin-3-yl)pyrrolidin-3-ol dihydrochloride (8 mg, 0.03 mmol). After 1 h at rt the crude product was purified by RP-HPLC. The pure fractions were basified (NaHCO3) and extracted with ethyl acetate, dried (Na2SO4), evaporated and dried in vacuum to yield the title compound (3 mg). MS (ESI, pos. ion) m/z: calcd for C21H21N3O4: 379.1532, found 379.1529.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[OH:11].[CH3:12][C:13]([CH3:21])(O)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].CS(O)(=O)=O>>[OH:11][C:4]1[C:5]([O:9][CH3:10])=[CH:6][C:7]([C:13]([CH3:21])([CH3:12])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:8][C:3]=1[O:2][CH3:1]
Reactant: CCCCCCC(C)(C)O
Reactant: COc1cccc(OC)c1O
Agent: CS(=O)(=O)O
Product: CCCCCCC(C)(C)c1cc(OC)c(O)c(OC)c1

Procedure:
The process of claim 1, said process comprising reacting 2,6-dimethoxyphenol with 1,1-dimethyl-1-heptanol in the presence of methanesulfonic acid to provide 1-hydroxy-2,6-dimethoxy-4-(1,1-dimethylheptyl)benzene; reacting said 1-hydroxy-2,6-dimethoxy-4-(1,1-dimethylheptyl)benzene with a halogenated disubstituted phosphite to provide a 2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl disubstituted phosphate; reacting said 2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl disubstituted phosphate with an alkali metal to afford 1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene; reacting said 1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene with boron tribromide to provide 5-(1,1-dimethylheptyl)-resorcinol, and recovering said 5-(1,1-dimethylheptyl)-resorcinol therefrom.
Reaction SMILES: [CH3:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH3:10])[C:5]([CH2:11][S:12]([C:14]2[N-:18][C:17]3[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:16]=3[N:15]=2)=[O:13])=[N:4][CH:3]=1.O.[Na+].C1(C(C2C=CC=CC=2)(O)[C@H](C2C=CC=CC=2)O)C=CC=CC=1>O>[CH3:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH3:10])[C:5]([CH2:11][S@@:12]([C:14]2[NH:15][C:16]3[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:17]=3[N:18]=2)=[O:13])=[N:4][CH:3]=1
Reactant: COc1ccc2[n-]c(S(=O)Cc3ncc(C)c(OC)c3C)nc2c1
Agent: O[C@@H](c1ccccc1)C(O)(c1ccccc1)c1ccccc1
Agent: [Na+]
Solvent: O
Product: COc1ccc2nc([S@@](=O)Cc3ncc(C)c(OC)c3C)[nH]c2c1

Procedure:
The formation of the inclusion complex can also be carried out from an aqueous solution of omeprazole sodium salt in the presence of a water-miscible solvent and (S)-1,1,2-triphenyl-1,2-ethanediol. Neutralisation with acid results in the formation of a suspension of the same inclusion complex (S)-omeprazole.2[(S)-1,1,2-triphenyl-1,2-ethanediol] which is isolated by filtration.