Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:13][CH2:14][OH:15])[C:7]2=[O:12].[OH-].[K+].I[CH2:19][CH3:20].C(OCC)C>CS(C)=O>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:13][CH2:14][O:15][CH2:19][CH3:20])[C:7]2=[O:12]
Reactant: O=C1c2cccc(Br)c2CCN1CCO
Reactant: CCI
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CS(C)=O
Product: CCOCCN1CCc2c(Br)cccc2C1=O
Reaction time: 0.5 h

Procedure:
0.363 g of 5-bromo-2-(2-hydroxyethyl)-3,4-dihydroisoquinolin-1(2H)-one is dissolved under an inert atmosphere in 3 cm3 of dimethylsulfoxide at a temperature close to 20° C. 98 mg of finely ground potassium hydroxide are added. The reaction mixture is stirred for 30 min at a temperature close to 20° C., then 0.131 cm3 of iodoethane is introduced. The stirring is continued for 20 h at a temperature close to 20° C. 50 cm3 of a water/ice mixture and 80 cm3 of ethyl ether are added. After decanting, the organic phase is washed with 3 times with 10 cm3 of water, 30 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated using a rotary evaporator under reduced pressure (5 kPa). 356 mg of 5-bromo-2-(2-ethoxyethyl)-3,4-dihydroisoquinolin-1(2H)-one are obtained in the form of a colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:10]([CH3:14])[C:11]([OH:13])=O)=[O:9])=[CH:4][CH:3]=1.[NH2:15][CH:16]1[C:31](=[O:32])[N:18]2[C:19]([C:28]([OH:30])=[O:29])=[C:20]([CH2:23][O:24][C:25](=[O:27])[NH2:26])[CH2:21][S:22][C@H:17]12>>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:10]([CH3:14])[C:11]([NH:15][CH:16]2[C:31](=[O:32])[N:18]3[C:19]([C:28]([OH:30])=[O:29])=[C:20]([CH2:23][O:24][C:25](=[O:27])[NH2:26])[CH2:21][S:22][C@H:17]23)=[O:13])=[O:9])=[CH:6][CH:7]=1
Reactant: CC(C(=O)O)S(=O)c1ccc(O)cc1
Reactant: NC(=O)OCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Product: CC(C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12)S(=O)c1ccc(O)cc1

Procedure:
428 mg. of 2-(p-hydroxyphenylsulfinyl)propionic acid and 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid were reacted in the same manner as described in Example 28 and 131 mg. of 7-[2-(p-hydroxyphenylsulfinyl)propionamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid were obtained.
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=O)[NH:20][C:21](=[O:35])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:46])=CC=1>O1CCOCC1>[CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=[S:46])[NH:20][C:21](=[O:35])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCOC(=O)c1coc(Cn2cc(C3c4ccc(C)cc4C=Cc4oc(CC)nc43)c(=O)[nH]c2=O)n1
Solvent: C1COCCO1
Product: CCOC(=O)c1coc(Cn2cc(C3c4ccc(C)cc4C=Cc4oc(CC)nc43)c(=S)[nH]c2=O)n1

Procedure:
A mixture of the product of step (i) (1.26 g) and Lawesson's reagent (1.56 g) in 1,4-dioxane (30 ml) was heated at reflux for 16 hours. The solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and saturated brine. The organic phase was collected, dried (MgSO4) and solvent evaporated under reduced pressure. Purification was by chromatography eluting with 50% ethyl acetate in toluene.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:24]([C:26]1[CH:27]=[C:28]([C:36](Cl)=[O:37])[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[CH:31][CH:30]=2)#[N:25]>C(Cl)Cl>[C:24]([C:26]1[CH:27]=[C:28]([C:36]([N:10]([CH2:9][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:12][CH:13]=[CH2:14])[CH3:11])=[O:37])[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[CH:31][CH:30]=2)#[N:25]
Reactant: N#Cc1cc(C(=O)Cl)c2ccccc2c1
Reactant: C=CCC(CNC)c1ccc(F)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCC(CN(C)C(=O)c1cc(C#N)cc2ccccc12)c1ccc(F)cc1
Yield: 80.5 %

Procedure:
[2-(4-Fluorophenyl)pent-4-en-1-yl]methylamine (1.0 g, 5.2 mmol) was dissolved in CH2Cl2 and stirred at 0° C. during addition of DIPEA (1.5 g, 11.4 mmol) and 3-cyano-1-naphthoyl chloride (Method 11; 1.1 g, 5.17 mmol). The mixture was stirred with cooling for a short while and then stirred at room temperature for 2 h. The mixture was washed twice with water, once with an aqueous solution of KHSO4, and then with brine. The solvent was removed by evaporation and the residue flash chromatographed on silica gel (methanol-CH2Cl2, 5:95). There was obtained 1.55 g (80%) of 3-cyano-N-[2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-1-naphthamide as an oil. 1H NMR (400 MHz, CDCl3): 2.1-4.9 (cm, 8H), 5.0-5.1 (m, 2H), 5.6-5.8 (m, 1H), 6.4-8.0 (cm, 9H), 8.2 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:33][CH3:34])=[C:6]([S:8]([N:11]2[C:16]3[CH:17]=[C:18]([C:21]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([C:30]([OH:32])=[O:31])=[N:28][CH:29]=4)=[O:22])[CH:19]=[CH:20][C:15]=3[O:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:7]=1.[CH2:35](OC(C1C=CC(N)=CN=1)=O)[CH3:36]>>[CH2:35]([O:31][C:30]([C:27]1[CH:26]=[CH:25][C:24]([NH:23][C:21]([C:18]2[CH:19]=[CH:20][C:15]3[O:14][CH2:13][CH2:12][N:11]([S:8]([C:6]4[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[O:33][CH3:34])(=[O:10])=[O:9])[C:16]=3[CH:17]=2)=[O:22])=[CH:29][N:28]=1)=[O:32])[CH3:36]
Reactant: CCOC(=O)c1ccc(N)cn1
Reactant: COc1ccc(Cl)cc1S(=O)(=O)N1CCOc2ccc(C(=O)Nc3ccc(C(=O)O)nc3)cc21
Product: CCOC(=O)c1ccc(NC(=O)c2ccc3c(c2)N(S(=O)(=O)c2cc(Cl)ccc2OC)CCO3)cn1

Procedure:
5-{[4-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-pyridine-2-carboxylic acid, MS (ISP): m/e=502.0, 503.9 (M−H), was prepared as described in example 1, steps 1 to 6. Step 5 was performed using 5-amino-pyridine-2-carboxylic acid ethyl ester and yielded 5-{[4-(5-chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-pyridine-2-carboxylic acid ethyl ester, which was hydrolyzed in step 6.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.C([O-])([O-])=O.[Cs+].[Cs+].[OH:19][CH2:20][C:21]1[CH:22]=[N:23][C:24]2[C:29]([C:30]=1[C:31]1[CH:32]=[C:33]([OH:37])[CH:34]=[CH:35][CH:36]=1)=[CH:28][CH:27]=[CH:26][C:25]=2[C:38]([F:41])([F:40])[F:39].Cl>C(OCC)(=O)C.C(Cl)Cl>[OH:19][CH2:20][C:21]1[CH:22]=[N:23][C:24]2[C:29]([C:30]=1[C:31]1[CH:32]=[C:33]([CH:34]=[CH:35][CH:36]=1)[O:37][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1)=[CH:28][CH:27]=[CH:26][C:25]=2[C:38]([F:41])([F:39])[F:40]
Reactant: O=C(O)Cc1ccc(CBr)cc1
Reactant: OCc1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(O)Cc1ccc(COc2cccc(-c3c(CO)cnc4c(C(F)(F)F)cccc34)c2)cc1
Temperature: 70 °C
Reaction time: 1 h

Procedure:
4-Bromomethylphenylacetic acid (1.86 g, 8.13 mmol) is taken into CH2Cl2 (80 mL) and to this is added Cs2CO3 (9.63 g, 29.56 mmol) and the mixture is stirred for 1 hour. Next, 3-[3-(hydroxymethyl)-8-(trifluoromethyl)quinolin-4-yl]phenol (2.36 g, 7.39 mmol) is added and the reaction is stirred overnight. The reaction is not complete, therefore an additional 3 g of 4-bromomethylphenylacetic acid and 2 g of Cs2CO3 is added and stirring is continued for another overnight period. The reaction is neutralized with HCl and then the solvent is removed. The resulting material is taken up into THF/MeOH/2N NaOH and heated at 70° C. for 45 minutes. The reaction is neutralized with HCl then the organics are removed and the aqueous layer is extracted with ethyl acetate. The combined organics is washed with water and brine and finally dried over Na2SO4. The resulting material is purified via column chromatography using 50% ethyl acetate in hexanes as the eluent to yield a white solid, which still contained an impurity. This material is dissolved into ethyl acetate and washed with saturated sodium bicarbonate. The ethyl acetate layer is concentrated to yield the desired product. HRMS: calcd for C26H20F3NO4+H, 468.14227; found (ESI, [M+H]+), 468.1428.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[O:18]1[CH2:20][CH:19]1[CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27]([C:31]#[N:32])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1.[Na+].[Cl-]>CN(C=O)C>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:20][CH:19]([OH:18])[CH2:21][N:22]2[C:30]3[C:25](=[CH:26][C:27]([C:31]#[N:32])=[CH:28][CH:29]=3)[CH:24]=[CH:23]2)=[CH:13][CH:12]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCOc1ccc(O)cc1
Reactant: N#Cc1ccc2c(ccn2CC2CO2)c1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCOc1ccc(OCC(O)Cn2ccc3cc(C#N)ccc32)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
0.13 g (2.47 mmol) sodium hydride as 60% dispersion in mineral oil is suspended in 10 ml absolute DMF under nitrogen, stirred at room temperature for 10 min and mixed with the solution of 0.5 g (2.39 mmol) 4-heptyloxyphenol in 5 ml absolute DMF. Having stirred for 1 hour, a solution of 475 mg (2.39 mmol) 1-oxiranylmethylindole-5-carbonitrile in 5 ml absolute DMF is added and stirring is continued at room temperature overnight. Thereafter, the suspension is hydrolyzed with semi-saturated NaCl solution and extracted three times with ethyl acetate. The extracts are washed with saturated NaCl solution, dried on sodium sulfate and the solvent is distilled off. The residue is purified on silica gel by means of column chromatography (flow agent: hexane/ethyl acetate 1:1), the product accruing as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:19][CH2:20][O:21][CH3:22])=[C:7]([CH:18]=1)[CH:8]=[N:9][C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][C:11]=1[OH:17].[CH3:23][O:24]C1C(OC)=CC(C=O)=C(OCOC)C=1>>[CH3:23][O:24][C:4]1[C:3]([O:2][CH3:1])=[CH:18][C:7]([CH:8]=[N:9][C:10]2[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][C:11]=2[OH:17])=[C:6]([O:19][CH2:20][O:21][CH3:22])[CH:5]=1
Reactant: COCOc1ccc(OC)cc1C=Nc1c(C)cccc1O
Reactant: COCOc1cc(OC)c(OC)cc1C=O
Product: COCOc1cc(OC)c(OC)cc1C=Nc1c(C)cccc1O

Procedure:
2-[(4,5-dimethoxy-2-methoxymethoxybenzylidene)amino]-3-methylphenol (F5) was prepared in a similar manner for the preparation of 2-[(5-Methoxy-2-methoxymethoxybenzylidene)amino]-3-methylphenol (F4) by using 4,5-dimethoxy-2-methoxymethoxybenzaldehyde (F2) (2.26 g, 10 mmol) instead of 5-methoxy-2-methoxymethoxybenzaldehyde (F1) in 86% (2.80 g): 1H-NMR (500 MHz, CDCl3) δ3.53 (s, 3H), 5.24 (s, 3H), 7.17 (d, 1H, J=9.0 Hz), 7.35 (d, 1H, J=9.0 Hz), 10.52 (s, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:8]=1)([O-])=O>CO.[Pd]>[O:12]1[CH2:11][CH2:10][CH:9]([N:7]2[CH:8]=[C:4]([NH2:1])[CH:5]=[N:6]2)[CH2:14][CH2:13]1
Reactant: O=[N+]([O-])c1cnn(C2CCOCC2)c1
Agent: [Pd]
Solvent: CO
Product: Nc1cnn(C2CCOCC2)c1
Yield: 95.1 %

Procedure:
A solution of 4-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole (568 mg, 2.88 mmol, 1 equiv) in methanol was circulated through a H-Cube® Continuous-flow hydrogenation reactor (ThalesNano) fitted with a palladium on carbon catalyst cartridge at 50° C. The collected solution was concentrated in vacuo to afford product as pink solid (458 mg, 95% yield). LCMS (ESI) m/z: 168.0.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=4)[C:12]=3[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]=2[CH3:35])[CH:5]=[CH:6][CH:7]=1.[C:36](Cl)(=[O:39])[CH2:37][CH3:38]>>[CH:23]([C:20]1[CH:21]=[CH:22][C:17]([CH:13]2[C:12]3[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]([CH3:35])=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:36](=[O:39])[CH2:37][CH3:38])[CH:3]=4)[C:16]=3[O:15][CH2:14]2)=[CH:18][CH:19]=1)([CH3:24])[CH3:25]
Reactant: Cc1c(NC(=O)CC(C)(C)C)c(C)c2c(c1-c1cccc(N)c1)OCC2c1ccc(C(C)C)cc1
Reactant: CCC(=O)Cl
Product: CCC(=O)Nc1cccc(-c2c(C)c(NC(=O)CC(C)(C)C)c(C)c3c2OCC3c2ccc(C(C)C)cc2)c1
Yield: 84 %

Procedure:
Using N-(7-(3-aminophenyl)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 122 and propionyl chloride, the title compound was obtained in the same manner as in Example 121. Yield: 84%. Melting point: 237-239° C. (ethyl acetate-hexane).
Reaction SMILES: I[C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH3:14])([CH3:13])[S:7](=[O:12])(=[O:11])[C:8]([CH3:10])([CH3:9])[C:4]=2[CH:3]=1.[SH:17][C:18]1[CH:19]=[C:20]([C:24]2([O:30][CH3:31])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:21]=[CH:22][CH:23]=1>>[CH3:31][O:30][C:24]1([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([S:17][C:2]3[CH:16]=[CH:15][C:5]4[C:6]([CH3:14])([CH3:13])[S:7](=[O:12])(=[O:11])[C:8]([CH3:10])([CH3:9])[C:4]=4[CH:3]=3)[CH:19]=2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1
Reactant: COC1(c2cccc(S)c2)CCOCC1
Reactant: CC1(C)c2ccc(I)cc2C(C)(C)S1(=O)=O
Product: COC1(c2cccc(Sc3ccc4c(c3)C(C)(C)S(=O)(=O)C4(C)C)c2)CCOCC1
Yield: 28 %

Procedure:
Using a similar procedure to that described in Example 12, 5-iodo-1,1,3,3-tetramethyl-1,3-dihydrobenzo[c]thiophene-2,2-dioxide was reacted with 4-(3-mercaptophenyl)-4-methoxytetrahydropyran to give 4-methoxy-4-[3-(1,1,3,3-tetramethyl-2,2-dioxo-1,3-dihydrobenzo[c]thien-5-ylthio)phenyl]tetrahydropyran in 28% yield, m.p. 133°-135° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([C:12]#[N:13])[CH2:4][CH2:3]1.[CH3:15]I>C(O)(C)(C)C>[CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:15])([C:12]#[N:13])[CH2:4][CH2:3]1
Reactant: CI
Reactant: CC1(C)CCC(C#N)c2ccccc21
Solvent: CC(C)(C)O
Product: CC1(C)CCC(C)(C#N)c2ccccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.6 %

Procedure:
81.5 g of 1,1-dimethyl-4-cyano-tetralin are added dropwise to 49 g of potassium tert.butylate in 400 ml of tert.butanol and the mixture is stirred at room temperature for 1 hour. At 5° C. there are then added dropwise 72 g of methyl iodide and the mixture is stirred for 15 hours without cooling. The bulk of the tert.butanol is distilled off, the residue is taken up in ether and washed neutral with water, dried over sodium sulphate and evaporated. The residue is distilled in vacuo and there are obtained 61 g of 1,1,4-trimethyl-4-cyano-tetralin of boiling point 85° C./0.25 mmHg; melting point 46° C.; yield 70%. Odour: resembling (3), but more intensive, woody.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([Cl:20])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:23]([O:26][C:27]1[CH:28]=[C:29]([CH:31]=[CH:32][C:33]=1[CH3:34])[NH2:30])(=[O:25])[CH3:24]>C(O)(C)C>[ClH:20].[C:23]([O:26][C:27]1[CH:28]=[C:29]([CH:31]=[CH:32][C:33]=1[CH3:34])[NH:30][C:14]1[C:13]2[C:18](=[CH:19][C:10]([O:9][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)=[C:11]([O:21][CH3:22])[CH:12]=2)[N:17]=[CH:16][N:15]=1)(=[O:25])[CH3:24]
Reactant: CC(=O)Oc1cc(N)ccc1C
Reactant: COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
Agent: Cl
Solvent: CC(C)O
Product: COc1cc2c(Nc3ccc(C)c(OC(C)=O)c3)ncnc2cc1OCc1ccccc1
Temperature: 25 °C
Yield: 89.2 %

Procedure:
A mixture of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (2.18 g, 6.47 mmol), 3-acetoxy-4-methylaniline (1.32 g, 8 mmol) and isopropanol (50 ml) was stirred and heated at reflux for 1 hour. The mixture was cooled to ambient temperature. The precipitate was filtered off, washed with isopropanol and ether to give 4-(3-acetoxy-4-methylanilino)-7-benzyloxy-6-methoxyquinazoline hydrochloride (2.69 g, 89%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][NH2:6].[C:11](Cl)(Cl)=[S:12].O>C(OCC)C>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][N:6]=[C:11]=[S:12]
Reactant: COc1ccccc1CN
Reactant: S=C(Cl)Cl
Solvent: O
Solvent: CCOCC
Product: COc1ccccc1CN=C=S
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.9 %

Procedure:
To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil.
Reaction SMILES: C([O:4][C@H:5]([CH3:32])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:20](=[O:21])[C:19]2[N:18]([CH3:22])[C:16](=[O:17])[N:15](COC(=O)C(C)(C)C)[C:14]=2[N:13]([CH3:31])[C:11]1=[O:12])(=O)C.C[O-].[Na+].Cl>CO>[OH:4][C@H:5]([CH3:32])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:20](=[O:21])[C:19]2[N:18]([CH3:22])[C:16](=[O:17])[NH:15][C:14]=2[N:13]([CH3:31])[C:11]1=[O:12]
Reactant: CC(=O)O[C@H](C)CCCCn1c(=O)c2c(n(C)c1=O)n(COC(=O)C(C)(C)C)c(=O)n2C
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: C[C@@H](O)CCCCn1c(=O)c2c([nH]c(=O)n2C)n(C)c1=O
Temperature: 25 °C
Reaction time: 96 h
Yield: 30.7 %

Procedure:
To a stirring solution of (R)-1-(5-acetoxyhexyl)-9-pivaloyloxymethyl-3,7-dimethyluric acid (0.10 g, 0.22 mmol) in methanol (5 ml) was added solid sodium methoxide (48 mg, 0.88 mmol) in one portion. After stirring at room temperature for 4 days, the mixture was treated with 5% aqueous hydrochloride acid solution (0.25 ml) and concentrated under a stream of nitrogen and mild heating. The residue was purified by preparative thin layer chromatography (250 micron silica gel plate) eluting with 7% methanol-dichloromethane to provide (R)-1(5-hydroxyhexyl)-3,7-dimethyluric acid (20 mg, 30% yield) as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25](B(O)O)[CH:26]=4)[C:21]([CH3:32])([CH3:31])[CH2:20]3)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[CH:33]1[C:38](Cl)=[N:37][C:36]([NH2:40])=[N:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([C:34]5[CH:33]=[CH:38][N:37]=[C:36]([NH2:40])[N:35]=5)[CH:26]=4)[C:21]([CH3:32])([CH3:31])[CH2:20]3)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(B(O)O)cc21
Reactant: Nc1nccc(Cl)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(-c3ccnc(N)n3)cc21
Temperature: 120 °C

Procedure:
Prepared according to procedure P using 1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid (92 mg, 0.215 mmol), PdCl2(PPh3)2 (15.12 mg, 0.021 mmol), 2-amine-4-chloropyrimidine (30.6 mg, 0.236 mmol) and sodium carbonate (68.3 mg, 0.644 mmol) in 1,4-dioxane (2.5 mL) and water (0.5 mL) and heating in the microwave for 1 h at 120° C. After purification 4-(1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-pyrimidinamine was obtained as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.68-8.80 (1H, m), 8.49 (1H, d, J=2.0 Hz), 8.26 (1H, d, J=5.5 Hz), 7.72-7.99 (4H, m), 7.41 (1H, ddd, J=7.0, 5.1, 2.0 Hz), 7.29-7.34 (1H, m), 6.93 (1H, d, J=5.1 Hz), 6.77-6.86 (1H, m), 5.16 (2H, br. s.), 3.77-3.95 (2H, m), 2.27-2.44 (3H, m), 1.61-1.68 (3H, m), 1.51-1.60 (3H, m). Mass Spectrum (ESI) m/e=478 (M+1).
Reaction SMILES: CC1C=C(OCCN2CCN(C)CC2)N([CH2:17][C:18]2[CH:23]=CC=C[CH:19]=2)N=1.[OH2:24]>>[C:18]([O:24][O:24][C:18]([CH3:17])([CH3:19])[CH3:23])([CH3:17])([CH3:19])[CH3:23]
Reactant: Cc1cc(OCCN2CCN(C)CC2)n(Cc2ccccc2)n1
Reactant: O
Product: CC(C)(C)OOC(C)(C)C
Yield: 0.5 %

Procedure:
As an example it can be mentioned that, with an apparatus including four infrared sources forming an infrared zone having a length of only 300 mm and having a peak value of the wave lengths around 1.2 μm, it has proved possible to produce tubes having a diameter of 15 mm and a wall thickness of 2.5 mm at a speed of 16.5 kg/h. The atmosphere in the oven was nitrogen mixed with air, that is, not an entirely inert atmosphere. The power of the infrared source furthermore was relatively limited. In spite of this the quality of these tubes with regard to dimensional stability, termal stability, surface finish and cross-linking approaches the quality of the tubes obtained with the slow process according to SE-B-324 450, whilst the speed of manufacture approaches the speed of manufacture for the "PEXEP"-method mentioned introductorily. In another example, tubes intended for tap water were manufactured with the same dimensions as the preceding ones with a dispensed mass of 35 kg/h at a melting temperature of about 175° C. and a total applied effect in two IR-zones having each four IR-lamps or 14-15 kW. With an admixture of 0.5% ditert.butylperoxide, cross-linking degrees of between 76 and 78% were obtained, which is well within the range of the desirable degree of cross-linking, 70-90%. The tubes at the same time displayed a very high surface finish both on the inside and on the outside.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH:14]([Si:17](Cl)([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])([CH3:16])[CH3:15].O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][N:8]([Si:17]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:14]([CH3:16])[CH3:15])[C:5]2=[N:6][CH:7]=1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Reactant: Clc1cnc2[nH]cc(I)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)[Si](C(C)C)(C(C)C)n1cc(I)c2cc(Cl)cnc21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 38.8 %

Procedure:
To 5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (2, 16.50 g, 59.25 mmol) in 250.0 mL of N,N-dimethylformamide, sodium hydride (3.10 g, 60% in mineral oil, 77.5 mmol) was added. The reaction was stirred at room temperature for 90 minutes, then triisopropysilyl chloride (3, 13.00 mL, 61.36 mmol) was added slowly. The reaction was stirred at room temperature overnight, then poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (4, 10.0 g). 5-fluoro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine is prepared similarly from 5-fluoro-3-iodo-1H-pyrrolo[2,3-b]pyridine.