Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH:19]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)[CH2:20][CH2:21][C:22]([OH:24])=O)[C:3](=[O:18])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6]([C:14]([F:17])([F:16])[F:15])[CH:5]=1.[CH:33]([C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)([CH3:35])[CH3:34].C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[CH:33]([C:36]1[CH:42]=[CH:41][C:39]([NH:40][C:22](=[O:24])[CH2:21][CH2:20][CH:19]([N:2]([CH3:1])[C:3](=[O:18])[C:4]2[CH:5]=[C:6]([C:14]([F:16])([F:15])[F:17])[CH:7]=[C:8]([C:10]([F:13])([F:11])[F:12])[CH:9]=2)[CH2:25][C:26]2[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=2)=[CH:38][CH:37]=1)([CH3:35])[CH3:34]
Reactant: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(CCC(=O)O)Cc1ccc(Cl)cc1
Reactant: CC(C)c1ccc(N)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)c1ccc(NC(=O)CCC(Cc2ccc(Cl)cc2)N(C)C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1
Reaction time: 18 h

Procedure:
A mixture consisting of 41.6 mg of 4-[N'-methyl-N'-(3,5-bistrifluoromethyl-benzoyl)-amino]-5-(4-chlorophenyl)-pentanoic acid, 12.8 mg of 4-isopropylaniline, 36.65 mg of propanephosphonic acid anhydride, 37 mg of triethylamine and 1.5 ml of methylene chloride is left to stand at room temperature for 18 hours. 0.5 ml of 1N potassium carbonate solution is then added and the mixture is shaken vigorously. After separation of the phases, the organic phase is separated off and concentrated by evaporation. In this way the title compound is obtained in the form of a white foam. Rf value=0.26 (ethyl acetate)
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16].S(O[CH2:29][CH:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1)(C1C=CC(C)=CC=1)(=O)=O>CC(N(C)C)=O>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[CH2:32][CH2:31]2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16]
Reactant: Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Reactant: Nc1ccc(O)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)N1CCC(COc2ccc(N)c([N+](=O)[O-])c2)CC1
Temperature: 90 °C
Yield: 54.2 %

Procedure:
Cesium carbonate (16.29 g, 50 mmoles, 2 equivalents) was added to a stirred solution of 4-amino-3-nitrophenol (3.85 g, 25 mmoles, 1 equivalent) and tert-butyl 4-(tosyloxymethyl)piperidine-1-carboxylate (10.16 g, 27.5 mmoles, 1.1 equivalent) in anhydrous DMA (25 mls). The stirred reaction mixture was then heated to 90° C. (thermostatically controlled heating mantle) for 22 hours. The reaction mixture was then allowed to cool to room temperature and was filtered through a plug of Celite. The reaction flask and the Celite were then washed with ethyl acetate (250 ml). The organic solution was then transferred to a separatory funnel and extracted with additional ethyl acetate (3×200 ml). The combined ethyl acetate solution was then washed with water (2×100 ml), saturated sodium chloride (2×100 ml), dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. This material was triturated with diethylether to give a crystalline solid which was filtered off, washed with ether to give 4.76 g of tert-butyl 4-((4-amino-3-nitrophenoxy)methyl)piperidine-1-carboxylate (yield=54%). 1H-NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 7.89 (d, 1H), 7.74 (d, 1H), 3.82 (d, 2H), 3.65 (m, 2H), 2.40 (s, 3H), 1.76 (m, 1H), 1.54 (m, 2H), 1.38 (s, 9H), 0.98 (m, 2H). MS (EI): 352 (MH+).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:11][CH:10]([CH3:12])[CH:9]2[CH:4]([CH2:5][CH:6]([CH3:13])[CH2:7][CH2:8]2)[NH:3]1.[CH2:15]1[O:17][CH2:16]1.[H][H]>C(O)CO>[OH:17][CH2:16][CH2:15][N:3]1[CH:4]2[CH:9]([CH2:8][CH2:7][CH:6]([CH3:13])[CH2:5]2)[CH:10]([CH3:12])[CH2:11][C:2]1([CH3:14])[CH3:1]
Reactant: C1CO1
Reactant: CC1CCC2C(C)CC(C)(C)NC2C1
Reactant: [H][H]
Solvent: OCCO
Product: CC1CCC2C(C)CC(C)(C)N(CCO)C2C1

Procedure:
1-(2'-hydroxyethyl)-2,2,4,7-tetramethyl decahydroquinoline was prepared. 75 grams of 2,2,4,7-tetramethyl decahydroquinoline in 50 milliliters of ethylene glycol was reacted with ethylene oxide added over a period of 14 hours at a reaction temperature of 200° C. The reactor mix was distilled to yield a liquid product which boiled at 102° C. at 0.1 mm of Hg and which was 98% pure as determined by vapor pressure chromatography. The infrared and NMR spectra were consistent with the desired product. Calculated contents for the formula C15H29NO are 75.26% carbon, 12.21% hydrogen, and 5.85% nitrogen while measured contents were 74.78% carbon, 12.30% hydrogen, and 5.50% nitrogen.
Reaction SMILES: [C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([N:10]=[C:11]=[O:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:19]([OH:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:19]([O:26][C:11](=[O:12])[NH:10][C:8](=[O:9])[CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C=NC(=O)C(c1ccccc1)c1ccccc1
Reactant: OCc1ccccc1
Product: O=C(NC(=O)C(c1ccccc1)c1ccccc1)OCc1ccccc1

Procedure:
The title compound, white solid, m.p. 100-101° C. and MS: m/e=345 (M+) was prepared in accordance with the general method of example 1 from diphenylacetyl isocyanate and benzyl alcohol.
Reaction SMILES: [C:1]([OH:12])(=[O:11])[C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[CH:3]=1.C([O-])(=O)C1C=CC=C(C([O-])=O)C=1.[K+].[K+].[Ag:27]>>[C:1]([O-:12])(=[O:11])[C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([O-:7])=[O:6])[CH:3]=1.[Ag+2:27]
Reactant: [Ag]
Reactant: O=C(O)c1cccc(C(=O)O)c1
Agent: O=C([O-])c1cccc(C(=O)[O-])c1
Agent: [K+]
Product: [Ag+2]

Procedure:
A reaction was carried out in the same manner as illustrated in Example 10 except that 100 g of isophthalic acid was used in place of the phthalic acid used in Example 10, whereby an aqueous solution of potassium isophthalate having a pH value of 10.2 and containing 10.0% by weight of a solid matter was obtained, which was then subjected to a double decomposition reaction conducted in the same manner as illustrated in Example 10 to obtain 230 g of silver isophthalate having a silver content of 51.5% by weight.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]#[N:11])[C:4]=2[CH:3]=[N:2]1.[OH-].[K+].[I:14]I>CN(C=O)C>[I:14][C:3]1[C:4]2[C:5]([C:10]#[N:11])=[CH:6][CH:7]=[CH:8][C:9]=2[NH:1][N:2]=1
Reactant: N#Cc1cccc2[nH]ncc12
Reactant: II
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: N#Cc1cccc2[nH]nc(I)c12
Temperature: 25 °C
Reaction time: 5 h
Yield: 67.3 %

Procedure:
To a mixture of 1H-indazole-4-carbonitrile (1.65 g, 11.1 mmol) in DMF (30 mL) was added KOH (1.86 g 33.3 mmol) and I2 (5.6 g 22.2 mmol). The mixture was stirred at RT for 5 h. The reaction mixture was quenched with water (100 mL) and extracted with EtOAc (200 mL). The extract was concentrated in vacuo to afford 3-iodo-1H-indazole-4-carbonitrile as white solid (2.01 g, 64.7%). MS (ESI): m/z=270 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([NH:15][C:16]3[CH:20]=[C:19]([CH3:21])[NH:18][N:17]=3)[C:12]([C:22]([F:25])([F:24])[F:23])=[CH:11][N:10]=2)[C:5]([CH3:26])=[CH:4][C:3]=1[CH:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(O)(=O)C.C([BH3-])#N.[Na+]>>[CH3:26][C:5]1[CH:4]=[C:3]([C@H:27]2[CH2:32][CH2:31][C@@H:30]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH2:29][CH2:28]2)[C:2]([CH3:1])=[CH:7][C:6]=1[NH:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:20]=[C:19]([CH3:21])[NH:18][N:17]=2)[C:12]([C:22]([F:23])([F:24])[F:25])=[CH:11][N:10]=1
Reactant: C1COCCN1
Reactant: Cc1cc(Nc2nc(Nc3cc(C)c(C4CCC(=O)CC4)cc3C)ncc2C(F)(F)F)n[nH]1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1cc(Nc2nc(Nc3cc(C)c([C@H]4CC[C@@H](N5CCOCC5)CC4)cc3C)ncc2C(F)(F)F)n[nH]1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 4-(2,5-dimethyl-4-(4-(5-methyl-1H-pyrazol-3-ylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)cyclohexanone (40 mg, 0.087 mmol), morpholine (15 μL, 0.174 mmol) and acetic acid (75 μL, 0.13 mmol) was stirred at room temperature for 1 h. Sodium cyanoborohydride (8.2 mg, 0.13 mmol) was added to the reaction and the reaction mixture was stirred overnight. The mixture was concentrated and purified by silica chromatography (MeOH/DCM 8:92) to afford N2-(2,5-dimethyl-4-(cis-4-morpholinocyclohexyl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; Rf: 0.50 (Silica; MeOH/DCM 8:92); ESMS m/z 530.3 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[C:13]([CH2:22][OH:23])=[N:12][C:11]=2[CH:24]([CH3:26])[CH3:25])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[NH:27]([C:31]([O-:33])=[O:32])[C:28]([O-:30])=O.[CH2:34](O)[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43].C(=O)=NC(Cl)=O>>[NH:27]([C:28]([O:23][CH2:22][C:13]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[C:10]([S:9][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=2)=[C:11]([CH:24]([CH3:26])[CH3:25])[N:12]=1)=[O:30])[C:31]([O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[O:32]
Reactant: CCCCCCCCCCO
Reactant: O=C([O-])NC(=O)[O-]
Reactant: CC(C)c1nc(CO)n(Cc2ccncc2)c1Sc1cc(Cl)cc(Cl)c1
Agent: O=C=NC(=O)Cl
Product: CCCCCCCCCCOC(=O)NC(=O)OCc1nc(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)n1Cc1ccncc1
Yield: 83 %

Procedure:
The compound 89 (245 mg, 0.6 mmol) was converted to the iminodicarboxylate with N-decanyloxycarbonyl isocyanate prepared from 1-decanol (175 mg, 1.10mmol) and N-chlorocarbonylisocyanate (106 mg, 1 mmol) in the same manner as the example 82 to give the compound 99 (315 mg, 83%). Mp. 105-107° C. Rf 0.39 (EtOAc). 1H-NMR (CDCl3): δH0.88 (3 H, t like, CH3), 1.25-1.30 (14 H, m, --CH2 --), 1.31 (6 H, d, J 6.9 Hz, (CH3)2CH), 1.62 (2 H, m, --CH2 --), 3.18 (1 H, sep, J 6.9 Hz, (CH3)2CH), 4.14 (2 H, t, J 6.9 Hz, CH2O), 5.23 (2H, s, NCH2), 5.31 (2H, s, OCH2), 6.71 (2H, d, J 1.8 Hz, arom 2- and 6-H), 6.77 (2 H, d-like, 4-pyridyl 2- and 6-H), 6.99 (1 H, bs, NH), 7.06 (1 H, t, J 1.8 Hz, arom 4-H), 8.45 (2 H, d-like, 4-pyridyl 3- and 5-H). IR(CHCl3)cm-1 : 3424 (NH), 1807 and 1739 (OOCNCOO). Elementary analysis (for C31H40N4O4SCl2) Calcd. : C, 58.58% H, 6.34% N, 8.81% S, 5.04% Cl, 11.15% Found: C, 58.57% H, 6.37% N, 8.77% S, 5.02% Cl, 10.88%
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][N:10]([CH3:22])[N:11]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]1=[O:21].CCCCCC>C1COCC1>[CH3:22][N:10]([CH3:9])[NH:11][C:19](=[O:20])[C:18]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:12](=[O:21])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CN(C)N1C(=O)c2ccccc2C1=O
Reactant: Br[Mg]c1ccccc1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CN(C)NC(=O)c1ccccc1C(=O)c1ccccc1
Temperature: -30 °C
Reaction time: 0.25 h
Yield: 80 %

Procedure:
A solution of phenylmagnesium bromide in THF (11.6 mmol) was slowly added to a solution of phthalimide 16 (10.5 mmol) in THF (110 ml) at −78 ° C. and stirred under argon for 15 minutes. The mixture was then progressively warmed to −30 ° C. for 1 hour. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) and the aqueous layer extracted with Et2O. The combined organic layers were washed with brine (20 ml), dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc:hexane, to give 80% yield of the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH2:9].[Br:10]Br>CO.C(O)(=O)C>[BrH:10].[Br:10][C:6]1[CH:5]=[C:4]([CH3:8])[C:3]([NH2:9])=[C:2]([Cl:1])[CH:7]=1
Reactant: BrBr
Reactant: Cc1cccc(Cl)c1N
Solvent: CC(=O)O
Solvent: CO
Product: Br
Product: Cc1cc(Br)cc(Cl)c1N

Procedure:
2-Chloro-6-methyl-phenylamine (5.00 g, 35.3 mmol) was dissolved in methanol (15 mL) and acetic acid was added (5 mL). The solution was chilled in an ice bath and a solution of bromine (1.8 mL) in acetic acid (15 mL) was added dropwise. After complete addition MeOH (5 mL) was added to dissolve the precipitated solid. The solvents were removed under reduced pressure and the residue was triturated with hexanes to provide the title compound as an off white solid (10.49 g, 99%). 1H NMR (300 MHz, MeOD): δ 7.42 (s, 1H), 7.28 (s, 1H), 2.42 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23])[CH2:6][N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH:8]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH2:26](Cl)[CH3:27].[CH2:29]([NH:31][CH2:32][CH3:33])[CH3:30]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23])[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([CH2:30][CH2:29][N:31]([CH2:26][CH3:27])[CH2:32][CH3:33])[CH2:9][CH:8]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCNCC
Reactant: CCCl
Reactant: COc1cc(CN2CCNCC2c2ccccc2)cc(OC)c1OC
Product: CCN(CC)CCN1CCN(Cc2cc(OC)c(OC)c(OC)c2)C(c2ccccc2)C1

Procedure:
1-(3',4',5'-Trimethoxy benzyl)-2-phenyl piperazine prepared according to Example 17, is alkylated by means of diethylamine ethylchloride by following the procedure described in Example 3c. The resulting reaction product is obtained in the form of yellow oil boiling at 200° C./0.03 mm. Hg.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.Cl[C:32](Cl)([O:34]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:43][C:44]1[O:48][N:47]=[C:46]([CH3:49])[CH:45]=1>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:32]([NH:43][C:44]1[O:48][N:47]=[C:46]([CH3:49])[CH:45]=1)=[O:34]
Reactant: Cc1cc(N)on1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2ncnc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: O
Product: COc1cc2ncnc(Oc3ccc(NC(=O)Nc4cc(C)no4)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 58.9 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (43 mg) was dissolved in chloroform (1.2 ml) and triethylamine (0.1 ml) to prepare a solution. A solution of triphosgene (20 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 5 min. Next, 5-amino-3-methylisoxazole (15 mg) was added thereto, and the mixture was further stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was subjected to separatory extraction with chloroform. The organic layer was concentrated, and the residue was then purified by chromatography (chloroform:acetone=2:1) to give the title compound (18.1 mg, yield 31%).
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]([F:7])=[C:4]([F:6])[F:5].[CH:10]([O:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][OH:21])[CH2:16][CH2:15]1)=[CH2:11].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[F:5][C:4]([F:6])([O:21][CH2:20][CH:17]1[CH2:18][CH2:19][CH:14]([CH2:13][O:12][CH:10]=[CH2:11])[CH2:15][CH2:16]1)[CH:3]([F:7])[C:2]([F:9])([F:8])[F:1]
Reactant: C=COCC1CCC(CO)CC1
Reactant: FC(F)=C(F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: C=COCC1CCC(COC(F)(F)C(F)C(F)(F)F)CC1
Temperature: 25 °C
Yield: 75.9 %

Procedure:
Hexafluoropropene (264 g, 1.76 mol) was added dropwise to a mechanically stirred mixture of 1,4-cyclohexanedimethanol vinyl ether (300 g, 1.76 mol), acetonitrile (600 mL), and K2CO3 (121 g, 0.88 mol), at 0° C. under N2. The reaction flask was placed in an ice bath to moderate the exothermic reaction during the addition of hexafluoropropene. After complete addition of hexafluoropropene, the reaction mixture was stirred for an additional hour at room temperature and filtered. The filtrate was added to 1.5 L water and mixed well. The lower layer formed was separated, washed with water (3×300 mL), and concentrated under reduced pressure (approximately 0.05 mm Hg) to afford 1,1,2,3,3,3-hexafluoro-1-{[4 (vinyloxymethyl)cyclo-hexyl]methoxy} propane(cis/trans mixture) as a colorless liquid (428 g, 76% yield); b.p. 55-60° C./0.05 mm Hg; Refractive Index 1.4145 at 23.7° C.; GC/MS: m/z at 320 for M+; 19F and 1H NMR spectral data are consistent with the structure.
Reaction SMILES: CN(C)[CH:3]=[C:4]([CH2:7][O:8][CH3:9])[CH:5]=[O:6].[OH-].[Na+].S(OC)([O:16][CH3:17])(=O)=O>CO.O>[CH3:17][O:16][CH:3]=[C:4]([CH2:7][O:8][CH3:9])[CH:5]=[O:6]
Reactant: COS(=O)(=O)OC
Reactant: COCC(C=O)=CN(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COC=C(C=O)COC
Temperature: 25 °C
Reaction time: 1 h
Yield: 41 %

Procedure:
A solution of 3-(dimethylamino)-2-(methoxymethyl)-2-propenal, (E)- and (Z)- (53.06 g, 0.37 mol) and sodium hydroxide solution (29.7 g, 50, 0.37 mol) in methanol (60 mL) is refluxed for 20 minutes and concentrated in vacuo to obtain a white solid. A solution of the solid in water (250 mL) is treated dropwise with dimethyl sulfate (46.75 g, 0.37 mol), stirred at room temperature for one hour and extracted with methylene chloride. The organic extract is dried over anhydrous sodium sulfate, concentrated in vacuo and distilled to give the title product as a colorless liquid (19.66 g, bp 80° C./0.5 mm Hg, 41% yield).
Reaction SMILES: [ClH:1].Br[C:3]1C=C(NC)C(N)=C[CH:8]=1.[Na].[N:13]1([C:19]2[N:20]=[C:21](CC(O)=O)[NH:22][C:23](=O)[CH:24]=2)[CH2:18]COC[CH2:14]1>CN(C=O)C.N1C=CC=CC=1>[ClH:1].[CH3:18][N:13]([CH3:14])[CH2:19][CH2:24][CH2:23][N:22]=[C:21]=[N:20][CH2:3][CH3:8]
Reactant: CNc1cc(Br)ccc1N
Reactant: O=C(O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: Cl
Agent: [Na]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: CCN=C=NCCCN(C)C

Procedure:
In a round-bottom flask, the 4-bromo-N2-methylbenzene-1,2-diamine hydrochloride prepared above (1.2 g) is placed in a mixture of DMF (10 ml) and pyridine (10 ml) with magnetic stirring, and then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (968 mg) and then the sodium salt of (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid, obtained in stage 2 of Example 1 (1.2 g) are added. The mixture thus obtained is stirred at ambient temperature (20° C.) overnight. After evaporation of the reaction medium, glacial acetic acid (20 ml) is added and the resulting mixture is brought to reflux (90 min). The reaction medium is concentrated, and taken up in dichloromethane and water at pH 8 (2N sodium hydroxide), so as to form a solid which is filtered off and washed with dichloromethane. The solid obtained is dissolved in methanol, adsorbed onto silica (7 g) and purified by chromatography. Purification is carried out on a silica column (50 g), elution being carried out with a mixture of dichloromethane and 9/1 dichloromethane/MeOH (with CV=75 ml; gradient: 4 CV DCM; 4 CV of 0 to 16% 9/1 DCM/MeOH; 8 CV of 16 to 20% 9/1 DCM/MeOH; 1 CV of 20 to 30% 9/1 DCM/MeOH). The fractions containing the expected compound are combined and evaporated under reduced pressure. 900 mg of 2-[(6-bromo-1-methyl-1H-benzimidazol-2-yl)methyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one are isolated, the characteristics of which are the following:
Reaction SMILES: [CH3:1][C:2]([C:5]([NH2:7])=[NH:6])([CH3:4])[CH3:3].Cl.[Cl:9][C:10](Cl)(Cl)[S:11]Cl.[OH-].[Na+]>ClCCl.O>[C:2]([C:5]1[N:7]=[C:10]([Cl:9])[S:11][N:6]=1)([CH3:4])([CH3:3])[CH3:1]
Reactant: ClSC(Cl)(Cl)Cl
Reactant: CC(C)(C)C(=N)N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)c1nsc(Cl)n1
Temperature: -15 °C
Reaction time: 3 h
Yield: 60 %

Procedure:
6.83 g (50.00 mmol) of tert-butylcarbamidine hydrochloride are dissolved in 60 ml of dichloromethane and treated with 8.37 g (45.00 mmol) of trichloromethanesulphenyl chloride, before the reaction mixture is cooled to −15° C. A solution of 10.00 g (250 mmol) of sodium hydroxide in 20 ml of water is added dropwise and the mixture obtained is stirred at AT for 3 h. After adding 50 ml of dichloromethane, extracting three times with water and drying the combined organic phases over MgSO4, the solvent is evaporated under vacuum. (5.81 g, 90% purity, 60% yield, log P (pH 2.3)=3.44).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[O:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][N:35]2[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]2)[CH2:29][CH2:28]1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:38]2[CH:37]=[N:36][N:35]([CH2:34][CH2:33][N:30]3[CH2:31][CH2:32][O:27][CH2:28][CH2:29]3)[CH:39]=2)[CH:3]=1)=[O:15]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)nc3c2cnn3C(C)C)c(=O)[nH]1
Reactant: OB(O)c1cnn(CCN2CCOCC2)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: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: Cc1cc(C)c(CNC(=O)c2cc(-c3cnn(CCN4CCOCC4)c3)nc3c2cnn3C(C)C)c(=O)[nH]1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (1 equiv.), (1-(2-morpholinoethyl)-1H-pyrazol-4-yl)boronic acid (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.) in 1,4-dioxane was purged with argon for 10 min. Then, 2 M Na2CO3 (3.6 equiv.) in water was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100° C. for 1 h. After completion of the reaction, water was added to it and extraction was carried out using EtOAc. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the desired compound. LCMS: 519.00 (M+1)+; HPLC: 97.07% (@ 254 nm) (Rt; 4.925; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.55 (s, 1H), 8.76 (t, 1H), 8.46 (s, 1H), 8.26 (s, 1H), 8.14 (s, 1H), 7.85 (s, 1H), 5.89 (s, 1H), 5.34-5.31 (m, 1H), 4.39 (d, 2H, J=4.8 Hz), 4.30 (t, 2H, J=6.8 Hz), 3.54 (m, 4H), 2.76 (t, 2H, J=6.4 Hz), 2.42 (m, 4H), 2.22 (s, 3H), 2.12 (s, 3H), 1.51 (d, 6H, J=6.4 Hz).