Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9](=O)[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Sn](CC=C)(CC=C)CC=C)C=C.[OH2:25]>[Sc]>[C:1]1([CH:7]([OH:25])[CH2:8][CH:9]=[CH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O
Reactant: CC(=O)CCc1ccccc1
Agent: C=CC[Sn](CC=C)(CC=C)CC=C
Agent: [Sc]
Product: C=CCC(O)c1ccccc1
Yield: 98 %

Procedure:
Water (0.25 ml) was added to this silica gel supporting scandium (75 mg), and while stirring, 4-phenyl-2-butanone (0.25 mmol) and tetraallyltin (0.125 mmol) were continuously added. The mixture was stirred at 40° C. for 24 hours. The mixture was returned to room temperature, and then was extracted four times by a decantation method using hexane. The solvent was distilled off under reduced pressure, and then the residue was purified by silica gel thin layer chromatography, to obtain the target product, 1-phenyl-3-buten-1-ol. Yield 98%.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[OH:15][CH2:16][CH:17]1[O:22][C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[O:19][CH2:18]1.[ClH:27]>>[ClH:1].[ClH:27].[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:3]2[C:2]([O:15][CH2:16][CH:17]3[O:22][C:21]4[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=4[O:19][CH2:18]3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:9][CH2:10]1
Reactant: OCC1COc2ccccc2O1
Reactant: CN1CCN(c2nccnc2Cl)CC1
Agent: Cl
Product: CN1CCN(c2nccnc2OCC2COc3ccccc3O2)CC1
Yield: 87 %

Procedure:
The title compound was prepared according to the procedure described in Example 90, Step 2, starting from 1-(3-chloro-2-pyrazinyl)-4-methylpiperazine (described in Example 169, Step I) and 2-hydroxymethyl-2,3-dihydro-1,4-benzodioxine. Yield 87%; mp 160-167° C. Anal. (C18H22N4O3.2 HCl) H, N; C: calcd, 52.06; found, 52.6.
Reaction SMILES: [C:1]1([C@@H:7]([NH:27]C(OC(C)(C)C)=O)[C:8]([NH:10][C@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[CH2:13][CH2:14][CH:15]=[C:16]3[C:20]([O:22]C(C)(C)C)=[O:21])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O>C(Cl)Cl.C1(OC)C=CC=CC=1>[C:1]1([C@@H:7]([NH2:27])[C:8]([NH:10][C@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[CH2:13][CH2:14][CH:15]=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)N[C@H]1C(=O)N2C(C(=O)OC(C)(C)C)=CCC[C@H]12)c1ccccc1
Solvent: COc1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H](C(=O)N[C@H]1C(=O)N2C(C(=O)O)=CCC[C@H]12)c1ccccc1
Temperature: 25 °C
Reaction time: 0.83 h
Yield: 70.9 %

Procedure:
In this Example, 280 mg. (0.59 mmole) of (±)-cis-7-[(R)-2-phenyl-2-t-butyloxycarbonylaminoacetamido]-2-t-butyloxycarbonyl-1-azabicyclo[4,2,0]oct-2-en-8-one obtained in Example 25 is dissolved in 2.5 ml of anhydrous methylene chloride and 2.5 ml of anisole, and 5.0 ml of trifluoroacetic acid is added under ice cooling. The mixture is allowed to stand for 4 hours and 50 minutes under ice cooling and is then concentrated. To the concentrated residue, 10 ml of ether is added and the mixture is stirred at room temperature for one hour to form a precipitate. The precipitate is collected by filtration to obtain 202 mg. (70.9%) of the desired compound as a pale yellow powder having the following properties.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>C(Cl)Cl>[CH3:20][S:21]([N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH2:8][CH2:9]1)(=[O:23])=[O:22]
Reactant: CS(=O)(=O)Cl
Reactant: O=[N+]([O-])c1ccc2c(c1)NCC2
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCc2ccc([N+](=O)[O-])cc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.4 %

Procedure:
In 50 ml of methylene chloride was dissolved 2.5 g of 6-nitroindoline, and then 6.37 ml of triethylamine was added thereto. Under ice cooling, 3.51 g of methanesulfonyl chloride was added dropwise, the reaction solution was stirred at room temperature for 3 hours, and then ice-water was added thereto, followed by 1 hour of stirring. The reaction solvent was removed by evaporation under reduced pressure, a 1M aqueous hydrochloric acid solution was added to the residue, and precipitated was filtrated off, whereby 3.52 g of 1-methylsulfonyl-6-nitroindoline was obtained as a brown solid.
Reaction SMILES: CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:34][C:35]([F:55])([C:48]1[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=1)[CH2:36][CH2:37][S:38][C:39]1[N:47]=[CH:46][CH:45]=[CH:44][C:40]=1[C:41]([OH:43])=O.[CH3:56][CH:57]([CH3:61])[CH2:58][CH2:59][NH2:60]>C(Cl)Cl.CC(=O)OCC.CCCCCC>[F:55][C:35]([F:34])([C:48]1[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=1)[CH2:36][CH2:37][S:38][C:39]1[C:40]([C:41]([NH:60][CH2:59][CH2:58][CH:57]([CH3:61])[CH3:56])=[O:43])=[CH:44][CH:45]=[CH:46][N:47]=1
Reactant: CC(C)CCN
Reactant: O=C(O)c1cccnc1SCCC(F)(F)c1ccc(F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)CCNC(=O)c1cccnc1SCCC(F)(F)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 54.3 %

Procedure:
320 μl (1.83 mmol) of DIPEA and 350 mg (0.91 mmol) of HATU were added at 0° C. to a solution of 150 mg (0.46 mmol) of 2-(3,3-difluoro-3-(4-fluorophenyl)propylthio)-nicotinic acid in DCM (10 ml). After stirring for 30 min at 0° C., 63 μl (0.55 mmol) of 3-methylbutan-1-amine were added and then the mixture was stirred for 16 h at RT. Dilution with water (20 ml) and extraction with DCM (2×20 ml) were then carried out. The combined organic phases were washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. CC (EA/hexane 7:3) of the residue yielded 100 mg (0.25 mmol, 55%) of 2-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]-sulfanyl]-N-(3-methyl-butyl)-pyridine-3-carboxylic acid amide. MS: m/z 397.1 [M+H]+.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[CH:16][C:17]3[CH:23]=[CH:22][CH2:21][N:20]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]5[O:32][CH2:33][O:34][C:28]=5[CH:27]=4)[C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])C.Cl.O>C(O)C>[C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[CH:16][C:17]3[CH:23]=[CH:22][CH2:21][N:20]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]5[O:32][CH2:33][O:34][C:28]=5[CH:27]=4)[C:18]=3[N:19]=2)[CH2:10][CH2:9]1)([OH:7])=[O:5]
Reactant: CCOC(=O)C1CCN(c2ncc3c(n2)N(NCc2ccc4c(c2)OCO4)CC=C3)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)C1CCN(c2ncc3c(n2)N(NCc2ccc4c(c2)OCO4)CC=C3)CC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 76.1 %

Procedure:
1.56 ml of 1N sodium hydroxide was added to a solution of 170 mg of 2-(4-ethoxycarbonylpiperidino)-8(3,4-methylenedioxybenzyl)aminopyrido[2,3-d]pyrimidine in 10 ml of ethanol. The obtained mixture was stirred at room temperature for 6 hours and neutralized by the addition of 1N hydrochloric acid and water. The crystals thus precipitated were recovered by filtration, whereby 121 mg of the title compound was obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][C@H:8]([CH:11]([CH3:13])[CH3:12])[CH2:9]O)=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21].CN(C)C=O.P(Br)(Br)([Br:29])=O.O>CC1C=CC=CC=1.C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][C@H:8]([CH:11]([CH3:13])[CH3:12])[CH2:9][Br:29])=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21]
Reactant: COCCCOc1cc(C[C@@H](CO)C(C)C)ccc1OC
Reactant: O=P(Br)(Br)Br
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: COCCCOc1cc(C[C@@H](CBr)C(C)C)ccc1OC
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 75.1 %

Procedure:
Dissolve (R)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl butanol (14.82 g, 50 mmol) and N,N-dimethyl formamide (0.4 g, 5.5 mmol) in methyl benzene (234 ml), add phosphorus oxybromide (15.05 g, 52.5 mmol) in droplets slowly, and control the temperature below 60° C. in that process; then, let them to react at 80° C. for 2 hours; cool down to room temperature, add water (234 ml), stir for 20 minutes, and separate the layers; extract the aqueous layer with petroleum ether for three cycles, combine the organic layers and wash twice with saturated sodium bicarbonate and saturated sodium chloride respectively; dry the organic layer with anhydrous sodium sulfate, filter, and condense the filtrate so as to obtain 17.2 g of oily matter. Add mixed solvent of ethyl acetate/normal hexane (17.2 ml/34.4 ml), control the product to crystallize at −10° C., filter, and treat the filter cake by vacuum drying at room temperature, so as to obtain 13.5 g of white solid matter; the yield is 75.1%, mp: 51-53° C., chiral purity: ≧99.9%.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:11](O)[CH3:12].S(=O)(=O)(O)O>C1(C)C=CC=CC=1>[OH:1][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ncccc1O
Reactant: CCO
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ncccc1O
Temperature: 95 °C
Yield: 73 %

Procedure:
To 3-hydroxypyridine-2-carboxylic acid (25 g, 179.5 mmol) in a 1 L dried flask was added 400 mL ethanol and 100 mL toluene followed by the addition of 10 mL sulfuric acid. The mixture was heated at reflux (95° C.) for 3 days. After cooling to rt, the mixture was concentrated to ¼ of its volume, and diluted with 600 mL ethyl acetate and 200 mL water. The aqueous layer was extracted with 200 mL ethyl acetate, and the combined organic layers were washed with sat NaHCO3 (3×200 mL), brine, and dried over Na2SO4. The solid was filtered off and the solvent was concentrated under reduced pressure to give 21.9 g of ethyl 3-hydroxypyridine-2-carboxylate (73%), which was used in the next step without purification. This ester (21.9 g, 131 mmol) was dissolved in pyridine and cooled to −40° C., followed by addition of trifluoromethanesulfonic anhydride (48 g, 170 mmol). The reaction mixture was then warmed to 0° C. for 30 min, and then warmed to rt for another 30 min. Water (100 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3×200 mL), and the combined organic layers were washed with sat sodium bicarbonate (200 mL), water (200 mL), brine (200 mL), and dried over sodium sulfate. The solid was filtered off, and the solvent was removed under reduced pressure to give 39 g (99%) of desired product, which was used in the next step without further purification. 1H NMR (300 MHz, CD2Cl2) δ 8.73 (dd, 1H), 7.72 (dd, 1H), 7.62 (dd, 1H), 4.46 (q, 2H), 1.42 (t, 3H).
Reaction SMILES: [NH2:1][C:2]1([CH2:15][OH:16])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[C:17](#[N:20])[CH:18]=[CH2:19]>C(O)C>[OH:16][CH2:15][C:2]1([NH:1][CH2:19][CH2:18][C:17]#[N:20])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1
Reactant: NC1(CO)CCN(Cc2ccccc2)CC1
Reactant: C=CC#N
Solvent: CCO
Product: N#CCCNC1(CO)CCN(Cc2ccccc2)CC1

Procedure:
A mixture of 4-amino-1-(phenylmethyl)-4-piperidinemethanol (0.0182 mol) and 2-propenenitrile (0.0304 mol) in ethanol (80 ml) was stirred and refluxed over the weekend. 2-Propenenitrile (2 ml) was added. The mixture was stirred and refluxed for 5 hours. 2-Propenenitrile (2 ml) was added again. The mixture was stirred and refluxed overnight. The solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The desired fractions were collected and the solvent was evaporated, yielding 3-[[4-(hydroxymethyl)-1-(phenylmethyl)-4-piperidinyl]amino]-propanenitrile (interm. 10).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[C:34]([C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH3:42])[CH:36]=4)=[CH:33][N:32]=[C:31]4[NH:43][CH:44]=[CH:45][C:30]=34)[CH2:25][CH2:24]2)=[O:22])[CH2:9][N:10]([CH:18]([CH3:20])[CH3:19])C(=O)OC(C)(C)C)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH2:9][NH:10][CH:18]([CH3:20])[CH3:19])[C:21]([N:23]2[CH2:24][CH2:25][N:26]([C:29]3[C:34]([C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH3:42])[CH:36]=4)=[CH:33][N:32]=[C:31]4[NH:43][CH:44]=[CH:45][C:30]=34)[CH2:27][CH2:28]2)=[O:22])=[CH:4][CH:3]=1
Reactant: COc1cccc(-c2cnc3[nH]ccc3c2N2CCN(C(=O)[C@H](CN(C(=O)OC(C)(C)C)C(C)C)c3ccc(Cl)cc3)CC2)c1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cccc(-c2cnc3[nH]ccc3c2N2CCN(C(=O)[C@H](CNC(C)C)c3ccc(Cl)cc3)CC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
(S)-tert-Butyl 2-(4-chlorophenyl)-3-(4-(5-(3-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.041 g, 0.065 mmol) was placed in DCM (3 mL) at room temperature. TFA (0.3 mL) was then added, and the reaction was stirred at room temperature for 1 hour. The reaction was then concentrated to dryness, dissolved in minimal DCM, and added dropwise to a stirring solution of 1M HCl in ether. The solid product was filtered, washed with ether, and dried to give (S)-2-(4-chlorophenyl)-3-(isopropylamino)-1-(4-(5-(3-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)propan-1-one (0.028 g, 81% yield) as the dihydrochloride salt. MS ESI (+) m/z 533 detected.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:4]=1[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][N:10]=[CH:9][N:8]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][C:21]=1[C:30]([F:33])([F:32])[F:31].N12CCN(CC1)CC2>C(#N)C>[CH3:1][O:2][C:3]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:4]=1[CH2:5][N:6]([C:7]1[CH:12]=[CH:11][N:10]=[CH:9][N:8]=1)[S:26]([C:23]1[CH:24]=[CH:25][C:20]([F:19])=[C:21]([C:30]([F:33])([F:31])[F:32])[CH:22]=1)(=[O:28])=[O:27]
Reactant: COc1ccc(CNc2ccncn2)c(OC)c1
Reactant: O=S(=O)(Cl)c1ccc(F)c(C(F)(F)F)c1
Agent: C1CN2CCN1CC2
Solvent: CC#N
Product: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2ccc(F)c(C(F)(F)F)c2)c(OC)c1
Yield: 32.9 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 14b by using the N-(2,4-dimethoxybenzyl)pyrimidin-4-amine (150 mg, 0.611 mmol) prepared in Example 14a, 4-fluoro-3-(trifluoromethyl)benzenesulfonyl chloride (321 mg, 1.22 mmol), 1,4-diazabicyclo[2.2.2]octane (137 mg, 1.22 mmol) and acetonitrile (5.0 mL), to yield the title compound (94.7 mg, 33%) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=O.C(O)(=O)[CH2:14][C:15]([OH:17])=[O:16].N1CCCCC1.Cl>N1C=CC=CC=1>[Cl:1][C:2]1[C:9]([Cl:10])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=[CH:14][C:15]([OH:17])=[O:16]
Reactant: O=C(O)CC(=O)O
Reactant: COc1ccc(C=O)c(Cl)c1Cl
Agent: Cl
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: COc1ccc(C=CC(=O)O)c(Cl)c1Cl
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A mixture of 2,3-dichloro-4-methoxybenzaldehyde (158 gm., 0.77 mole), malonic acid (146 gm., 1.4 mole), pyridine (450 ml.) and piperidine (15 ml.) is heated and stirred on a steam bath for 23/4 hours. The hot reaction mixture is poured, with stirring into a mixture of concentrated hydrochloric acid (770 ml.) and crushed ice (3.1 kg.).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[O:10][C:3]=12.[F:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][C:29]=1[C:30](=[O:35])[NH:31][CH2:32][CH2:33][OH:34]>>[F:23][C:24]1[CH:25]=[C:26]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([C:11]4[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=4)[O:10][C:3]=23)[CH:27]=[CH:28][C:29]=1[C:30]([NH:31][CH2:32][CH2:33][OH:34])=[O:35]
Reactant: O=C(NCCO)c1ccc(B(O)O)cc1F
Reactant: COc1cc(-c2cc3nccc(Cl)c3o2)cc(OC)c1OC
Product: COc1cc(-c2cc3nccc(-c4ccc(C(=O)NCCO)c(F)c4)c3o2)cc(OC)c1OC

Procedure:
The title compound was prepared by procedure C using 7-chloro-2-(3,4,5-trimethoxyphenyl)furo[3,2-b]pyridine (45.00 mg; 0.14 mmol; 1.00 eq.) instead of 7-chloro-2-iodo-furo[3,2-b]pyridine, and 3-fluoro-4-[(2-hydroxyethyl)-carbamoyl]benzeneboronic acid (35.14 mg; 0.15 mmol; 1.10 eq.) instead of 4-fluorophenylboronic acid and was obtained as a pale yellow solid (32 mg, 48%). (HPLC (method F): 99%, RT: 3.09 min); 1H NMR (500 MHz, DMSO-d6) δ [ppm] 8.60 (dd, J=5.1, 1.8, 1H), 8.38 (s, 1H), 8.12-8.06 (m, 2H), 7.89 (t, J=7.9, 1H), 7.79 (d, J=1.8, 1H), 7.71 (dd, J=5.1, 1.8, 1H), 7.33 (d, J=1.7, 2H), 4.80-4.73 (m, 1H), 3.92 (d, J=1.7, 6H), 3.74 (d, J=1.8, 3H), 3.57-3.51 (m, 2H), 3.37 (dd, J=12.0, 6.1, 2H); MS (m/z) 467 [M+H]+, RT: 3.0 min.
Reaction SMILES: [P].C([P+](CO)(CO)CO)[OH:3].C([P+](CO)(CO)CO)O.[O-:20][S:21]([O-:24])(=[O:23])=[O:22].[Cl-].[Na+:26]>>[S:21]([O-:24])([O-:23])(=[O:22])=[O:20].[Na+:26].[Na+:26].[OH-:3].[Na+:26]
Reactant: OC[P+](CO)(CO)CO
Agent: O=S(=O)([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Product: [OH-]

Procedure:
A phosphorus-containing condensation product was synthesized using 500 g. of 80 % THPS and 25 g. of sodium chloride in the same way as in I-A. Sodium sulfate which formed during synthesis of this condensation product and at neutralization of the agent with sodium hydroxide was removed by filtration before treating the fabric. Treatment was carried out using this condensation product under the same conditions as in Experiment No. 7 of Example 2, with the result that a good hand and excellent flame retardancy which passes the DOCFF 3-71 standard after 50 times washing were obtained.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH2:16][CH3:17])[NH:5][C:4](=[O:18])[CH:3]=1.[C:19](OC(=O)C)(=[O:21])[CH3:20]>>[C:19]([NH:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH2:16][CH3:17])[NH:5][C:4](=[O:18])[CH:3]=1)(=[O:21])[CH3:20]
Reactant: CC(=O)OC(C)=O
Reactant: CCCOc1ccccc1-c1nc(N)cc(=O)[nH]1
Product: CCCOc1ccccc1-c1nc(NC(C)=O)cc(=O)[nH]1

Procedure:
A stirred solution of 6-amino-2-(2-propoxyphenyl)-pyrimidin-4[3H]-one (0.5 g) and acetic anhydride was heated under reflux for 2.5 hours. The cooled reaction mixture was evaporated under reduced pressure to yield a residue which was washed with water and recrystallised twice from methanol to yield the title compound, 0.29 g, m.p. 230°-1° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]([C:13](=O)[CH2:14][CH3:15])=[C:11](O)[C:10](=[O:18])[N:9]2[C:19]2[CH:20]=[C:21]([CH3:27])[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)=[CH:4][CH:3]=1.[NH:28]([C:30]1[N:34]([CH3:35])[N:33]=[CH:32][CH:31]=1)[NH2:29]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3[C:13]([CH2:14][CH3:15])=[N:29][N:28]([C:30]4[N:34]([CH3:35])[N:33]=[CH:32][CH:31]=4)[C:11]=3[C:10](=[O:18])[N:9]2[C:19]2[CH:20]=[C:21]([CH3:27])[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)=[CH:4][CH:3]=1
Reactant: Cn1nccc1NN
Reactant: CCC(=O)C1=C(O)C(=O)N(c2cc(C)c(=O)n(C)c2)C1c1ccc(Cl)cc1
Product: CCc1nn(-c2ccnn2C)c2c1C(c1ccc(Cl)cc1)N(c1cc(C)c(=O)n(C)c1)C2=O

Procedure:
The title compound was prepared in analogy to the procedure described in Example 57 using 5-(2-(4-chlorophenyl)-4-hydroxy-5-oxo-3-propionyl-2,5-dihydro-1H-pyrrol-1-yl)-1,3-dimethylpyridin-2(1H)-one (Step 89.1) and 5-hydrazinyl-1-methyl-1H-pyrazole (Step 74.2). The crude material was first purified by silica gel column chromatography (1% ammonia/5% MeOH/CH2Cl2) followed by preparative achiral SFC (column 4-Ethyl-pyridine, gradient 10-15% in 6 min_total 11 min) and trituration in Et2O. tR: 1.01 min (LC-MS 2); ESI-MS: 463 [M+H]+ (LC-MS 2); Rf=0.42 (1% ammonia/5% MeOH/CH2Cl2); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97 (t, J=7.6 Hz, 3H) 1.94 (s, 3H) 2.35-2.48 (m, 2H) 3.37 (s, 3H) 3.86 (s, 3H) 6.25 (s, 1H) 6.63 (d, J=2.0 Hz, 1H) 7.34-7.48 (m, 5H) 7.58 (d, J=1.9 Hz, 1H) 7.75 (d, J=2.4 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7](=[O:9])[CH3:8].[Cl-:10].[Li+]>CN(C)C=O.O.[Cu](Cl)Cl>[Cl:10][CH:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:7](=[O:9])[CH3:8]
Reactant: COCCCCC(C)=O
Reactant: [Cl-]
Agent: Cl[Cu]Cl
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: O
Product: COCCCC(Cl)C(C)=O
Temperature: 85 °C
Reaction time: 1 h

Procedure:
1.5 mol of 6-methoxyhexan-2-one [29006-00-6] are added to a mixture of 3.6 mol of copper(II) chloride hydrate and 1.8 mol of lithium chloride in 900 ml of N,N-dimethylformamide at 80° C. The reaction mixture is stirred at 80-90° C. for 1 hour. 900 g of ice are added, and the precipitate is dissolved by adding N,N-dimethylformamide. Extraction with pentane (6×) is carried out. The combined organic phases are washed with water, dried over sodium sulphate and fractionated in vacuo. The title compound is identified by means of the Rf.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:5]([C:6]#[N:7])=[C:4]([CH3:17])[N:3]=1.NC1N=C(C)C(CN[C:28]([C:30]2[CH:31]=[N:32][N:33]([CH2:35][C:36]3[CH:41]=[CH:40][C:39](OC)=[CH:38][CH:37]=3)[CH:34]=2)=[O:29])=C(C)C=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCO.CO.CN(C1C=CN=CC=1)C.[Ni].C1COCC1>[NH2:1][C:2]1[N:3]=[C:4]([CH3:17])[C:5]([CH2:6][NH:7][C:28]([C:30]2[CH:31]=[N:32][N:33]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:34]=2)=[O:29])=[C:8]([O:10][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)[CH:9]=1
Reactant: Cc1nc(N)cc(OC2CCCCC2)c1C#N
Reactant: COc1ccc(Cn2cc(C(=O)NCc3c(C)cc(N)nc3C)cn2)cc1
Agent: [Ni]
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Solvent: CO
Product: Cc1nc(N)cc(OC2CCCCC2)c1CNC(=O)c1cnn(Cc2ccccc2)c1
Reaction time: 72 h

Procedure:
To a mixture of 6-Amino-4-(cyclohexyloxy)-2-methylnicotinonitrile (30.0 mg, 0.130 mmol) in EtOH (5 ml) were added about 10 cm3 of a Raney-Ni suspension in MeOH under Ar. The flask was sealed, and the suspension was vigorously stirred at it for 3 d under an atmosphere of hydrogen. The reaction mixture was filtered over a plug of cellite and eluted with DCM-MeOH (9:1, 100 ml), DCM (50 ml), MeOH (50 ml) and NH3 in MeOH (7N, 50 ml). The combined filtrates were concentrated. Dry THF (5 ml), 1-benzyl-1H-pyrazole-4-carboxylic acid (26.3 mg, 0.130 mmol, prepared in analogy to example 13), DIPEA (0.091 ml, 0.520 mmol), DMAP (0.80 mg, 0.0065 mmol) and HATU (49.4 mg, 0.130 mmol) were added, and the reaction mixture was stirred at it for 10 h, before it was concentrated to dryness. The crude product was purified by column chromatography (CombiFlash Companion, 4 g SiO2, DCM to DCM:MeOH 9:1), followed by preparative HPLC (Waters Sunfire Prep C18 OBD 5 um, 100×19 mm, A: H2O+0.1% TFA, B: MeCN+0.1% TFA, 15-45% B in 10 min, 30 ml/min, rt) affording the title compound. 1H-NMR (DMSO-d6, 400 MHz): 1.15-1.27 (m, 1H), 1.27-1.38 (m, 2 H), 1.40-1.50 (m, 1H), 1.51-1.62 (m, 2H), 1.62-1.72 (m, 2H), 1.77-1.88 (m, 2 H), 2.44 (s, 3H), 4.24 (d, 2H), 4.47 (mc, 1H), 5.34 (s, 2H), 6.29 (s, 1H), 7.19-7.25 (m, 2H), 7.27-7.41 (m, 5H), 7.84 (s, 1H), 7.92 (t, 1H), 8.21 (s, 1H), 12.81 (s, 1H); LCMS RtK=1.11 min, [M+H]+=420.4.