Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.N=C=N.[CH2:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O)C(N)(CO)CO>C(Cl)Cl>[CH2:29]([NH:36][C:13]([C:10]1[CH:11]=[N:12][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][CH:9]=1)=[O:15])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=C(O)c1cnc(-c2ccccc2)nc1
Reactant: NCc1ccccc1
Agent: N=C=N
Agent: NC(CO)(CO)CO
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: O=C(NCc1ccccc1)c1cnc(-c2ccccc2)nc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 2-phenyl-pyrimidine-5-carboxylic acid, (80 mg), 1-hydroxybenzotriazole (92 mg) and polymer supported-carbodiimide (640 mg, 1.25 mmol/g) in 8 mL of DCM is shaken at room temperature for 30 min and benzylamine (43 mg) is added. After shaking at room temperature for 1.5 days, PS-trisamine (295 mg, 4.08 mmol/g) is added. The mixture is continually shaken at room temperature for 16 hours. The solid is filtered and washed with DCM. The filtrate is concentrated to yield of 2-phenyl-pyrimidine-5-carboxylic acid benzylamide (98 mg, 85%) as a solid. MS: 290 (M+H); 1H NMR (CDCl3): 9.17 (s, 2H), 8.50 (d, 2H), 7.52-7.55 (m, 3H), 7.36-7.40 (m, 5H), 6.54 (broad, H), 4.69-4.71 (d, 2H); IC50=10 nM.
Reaction SMILES: [Br:1]/[CH:2]=[CH:3]/[CH:4]([OH:12])[C:5]([CH3:11])([CH3:10])[CH2:6][CH2:7][CH2:8][CH3:9].[C:13]1([C:19](Br)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[Br:1]/[CH:2]=[CH:3]/[CH:4]([O:12][C:19]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:5]([CH3:11])([CH3:10])[CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCC(C)(C)C(O)/C=C/Br
Reactant: BrC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: CCCCC(C)(C)C(/C=C/Br)OC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
Treatment of 1.88 g. (8 moles) of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8 moles) of triphenylmethyl bromide in 20 ml. of pyridine and purification of Florisil®, all as described in Example 728 gives the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]([CH2:20][CH2:21][CH3:22])[C:11]3[C:16]([C:17]=2[CH3:18])=[CH:15][C:14]([OH:19])=[CH:13][CH:12]=3)=[CH:5][CH:4]=1.[CH2:23]([O:25][C:26](=[O:31])[C:27](Br)([CH3:29])[CH3:28])[CH3:24]>>[CH2:23]([O:25][C:26](=[O:31])[C:27]([O:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:20][CH2:21][CH3:22])[C:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[C:17]2[CH3:18])([CH3:29])[CH3:28])[CH3:24]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: CCCn1c(-c2ccc(OC)cc2)c(C)c2cc(O)ccc21
Product: CCCn1c(-c2ccc(OC)cc2)c(C)c2cc(OC(C)(C)C(=O)OCC)ccc21

Procedure:
In accordance with a procedure analogous to that of Example 10, the above compound was prepared from 2-(4-methoxy-phenyl)-3-methyl-1-propyl-1H-indole-5-ol and 2-bromo-2-methyl-propanoic acid ethylester.
Reaction SMILES: [CH3:1][N:2]([C:4]([N:6]=[C:7]([NH2:9])[NH2:8])=[NH:5])[CH3:3].Cl.[OH-].[Na+].[CH:13](=O)[CH3:14]>O.CO>[NH2:8][C:7]1[NH:6][C:4]([N:2]([CH3:3])[CH3:1])=[N:5][CH:13]([CH3:14])[N:9]=1
Reactant: CC=O
Reactant: CN(C)C(=N)N=C(N)N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC1N=C(N)NC(N(C)C)=N1
Temperature: 25 °C
Reaction time: 1.67 h
Yield: 84 %

Procedure:
A 4 L two neck flask charged with 662 g (4 mol) metformin HCl and 1600 mL MeOH was stirred with a magnetic bar at 750 rpm at room temperature with a water bath. To this suspension was added sodium hydroxide 160 g (4 mol) in 200 mL water through one dropping funnel. At the same time acetaldehyde 226 mL (4 mol) in 400 mL of MeOH in another funnel was added to the mixture. The addition of NaOH solution finished in 70 minutes whereas the addition of acetaldehyde finished in 100 minutes. Then, the reaction mixture was filtered through celite to remove the sodium chloride. The solution was concentrated to give a white solid that was extracted with 1.2 L of hot ethanol to give a suspension. After filtration, the ethanol solution was concentrated to give a pale yellow solid, 520 g, yield is 84%.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[CH3:12][NH:13][CH2:14][CH2:15][OH:16].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C>[NH2:7][C:6]1[CH:8]=[C:2]([N:13]([CH3:12])[CH2:14][CH2:15][OH:16])[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: CNCCO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CN(CCO)c1ccc([N+](=O)[O-])c(N)c1
Temperature: 125 °C
Reaction time: 24 h
Yield: 88.2 %

Procedure:
A mixture of 5-chloro-2-nitroaniline (5 g, 29 mmol), 2-Methylamino-ethanol (7 mL, 87 mmol) and anhydrous potassium carbonate (5.3 g, 38 mmol) in N,N-dimethylacetamide (10 ml) were stirred at 125° C. under nitrogen for 1 day. Sample NMR analysis showed complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured onto cold water (30 mL), stirred vigorously and incubated at 4° C. overnight. The resulting yellow precipitate was collected by filtration, washed well with water then dried on the filter funnel. This was then slurried in diethyl ether, filtered, washed with additional diethyl ether, dried to afford 2-[(3-Amino-4-nitro-phenyl)-methyl-amino]-ethanol (5.4 g, 88% yield) as a yellow solid and used in the next step without further purification.
Reaction SMILES: C[O:2][C:3](=[O:49])[CH:4]([NH:25][C:26](=[O:48])[C:27]1[CH:32]=[C:31]([Br:33])[CH:30]=[CH:29][C:28]=1[NH:34][S:35]([C:38]1[CH:43]=[CH:42][C:41]([C:44]([CH3:47])([CH3:46])[CH3:45])=[CH:40][CH:39]=1)(=[O:37])=[O:36])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:8][CH:7]=1.[Li+].[OH-]>>[Br:33][C:31]1[CH:30]=[CH:29][C:28]([NH:34][S:35]([C:38]2[CH:39]=[CH:40][C:41]([C:44]([CH3:47])([CH3:46])[CH3:45])=[CH:42][CH:43]=2)(=[O:37])=[O:36])=[C:27]([CH:32]=1)[C:26]([NH:25][CH:4]([CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][CH:11]=1)[C:3]([OH:49])=[O:2])=[O:48]
Reactant: COC(=O)C(Cc1ccc(-c2ccccc2Oc2ccccc2)cc1)NC(=O)c1cc(Br)ccc1NS(=O)(=O)c1ccc(C(C)(C)C)cc1
Agent: [Li+]
Agent: [OH-]
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2ccc(Br)cc2C(=O)NC(Cc2ccc(-c3ccccc3Oc3ccccc3)cc2)C(=O)O)cc1
Yield: 86.5 %

Procedure:
2-[5-Bromo-2-(4-t-butyl-benzenesulfonylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)propionic acid methyl ester (0.04 g, 0.054 mmol) was treated with LiOH (2 eq, 1N aqueous solution) according to the general procedure C to give 0.034 g (87.0%) of 2-[5-Bromo-2-(4-t-butyl-benzenesulfonylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)propionic acid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7](Cl)=[N:8][OH:9].[Cl:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([C:21]#[CH:22])[CH:20]=1)[C:16]#[N:17].N>>[Cl:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([C:21]2[O:9][N:8]=[C:7]([C:6]3[CH:5]=[N:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH:22]=2)[CH:20]=1)[C:16]#[N:17]
Reactant: C#Cc1cc(Cl)cc(C#N)c1
Reactant: ON=C(Cl)c1cncc(F)c1
Agent: N
Product: N#Cc1cc(Cl)cc(-c2cc(-c3cncc(F)c3)no2)c1

Procedure:
The titled compound was prepared according to Method CB using the product of Example 28B (88 mg, 0.5 mmol) and the product of Example 66A (82 mg, 0.5 mmol). 1H NMR (300 MHz, MeOH-d4) δ 8.00 (s, 1H), 8.22 (ddd, J=9.5, 2.7, 1.7 Hz, 1H), 8.26 (dd, J=2.0, 1.4 Hz, 1H), 8.33 (t, J=1.7 Hz, 1H), 8.40 (t, J=1.5 Hz, 1H), 8.79 (d, J=2.7 Hz, 1H), 8.98 (t, J=1.7 Hz, 1H) ppm; MS (DCI/NH3) m/z 300 (M+H)+, 302 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.[CH:11]1([NH2:14])[CH2:13][CH2:12]1>>[CH:11]1([NH:14][C:8]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=2)=[O:10])[CH2:13][CH2:12]1
Reactant: NC1CC1
Reactant: O=C(O)c1cccc(Br)n1
Product: O=C(NC1CC1)c1cccc(Br)n1

Procedure:
Prepared according to the procedure described in Example 121, Step 1, using 6-bromo-pyridine-2-carboxylic acid and cyclopropylamine.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]1.C(N(CC)CC)C.[C:16]([Si:20]([CH3:23])([CH3:22])Cl)([CH3:19])([CH3:18])[CH3:17]>C(Cl)Cl>[C:16]([Si:20]([CH3:23])([CH3:22])[O:8][CH2:7][CH:3]1[CH2:4][CH2:5][CH2:6][NH:1][CH2:2]1)([CH3:19])([CH3:18])[CH3:17]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCC1CCCNC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCC1CCCNC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 60.5 %

Procedure:
To a solution of piperidin-3-ylmethanol (2.10 g, 0.018 mol) in CH2Cl2 (20 mL) is added triethylamine (5.53 g, 0.0547 mol) followed by t-butyldimethylchlorosilane (4.127 g, 0.0275 mol) and the reaction mixture is stirred at room temperature. After 24 hours, the reaction mixture is washed with water, saturated solution of NaHCO3, and brine. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) over a gradient using 0-10% MeOH in dichloromethane to afford the title compound (2.50 g, 60%). Mass spectrum (m/z): 231.2 (M+1).
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14](/[CH:16]=[CH:17]/[C:18]3[O:22][CH:21]=[CH:20][CH:19]=3)=O)=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.Cl.[NH2:24][OH:25].[OH-].[Na+]>>[O:22]1[CH:21]=[CH:20][CH:19]=[C:18]1[C:17]1[O:25][N:24]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([O:7][C:4]3[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=3)=[CH:9][CH:10]=2)[CH:16]=1
Reactant: NO
Reactant: O=C(/C=C/c1ccco1)c1ccc(Oc2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: c1ccc(Oc2ccc(-c3cc(-c4ccco4)on3)cc2)cc1

Procedure:
To a mixture of 3-furan-2-yl-1-(4-phenoxy-phenyl)-propenone (0.4 g, 1.4 mmol) and hydroxylamine hydrochloride (0.14 g, 2.1 mmol), was added sodium hydroxide (0.11 g, 2.8 mmol). The reaction mixture was heated to reflux for 3 days. The mixture was then concentrated, and neutralized with diluted HCl. Ethyl acetate and water were added. The organic layer was separated and dried over sodium sulfate. The solvent was removed and the residue was purified by column chromatography (silica, eluted with 20% ethyl acetate/hexanes) to give the desired isoxazole in poor yield (10 mg).
Reaction SMILES: O[CH2:2][N:3]1[C:8](=[O:9])[N:7]2[CH:10]=[N:11][C:12]([C:13]([NH2:15])=[O:14])=[C:6]2[N:5]=[N:4]1.BrC[C:18]#[C:19][Si:20]([CH3:23])([CH3:22])[CH3:21].C1CCN2C(=NCCC2)CC1.Cl>C(#N)C>[O:9]=[C:8]1[N:3]([CH2:2][C:18]#[C:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:4]=[N:5][C:6]2=[C:12]([C:13]([NH2:15])=[O:14])[N:11]=[CH:10][N:7]12
Reactant: C[Si](C)(C)C#CCBr
Reactant: NC(=O)c1ncn2c(=O)n(CO)nnc12
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: C[Si](C)(C)C#CCn1nnc2c(C(N)=O)ncn2c1=O
Reaction time: 0.5 h

Procedure:
To a cooled solution of 3-(Hydroxymethyl)-4-oxo-3,4-dihydroimidazo[5,1-][1,2,3,5]tetrazine-8-carboxamide (MM-001) (1 equiv) in acetonitrile (0.17 M concentration substrate in solvent) was added 3-bromo-1-(trimethylsilyl)-1-propyne (4 equivs) and DBU (1.4 equivs). The mixture was stirred at this temperature for 30 minutes whereupon it was acidified with 1 N HCl. The mixture was extracted with EtOAc (3×1 reaction volume). The combined organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to give an oily residue which was then precipitated from Et2O and washed with further Et2O to give the title compound. 1H NMR (400 MHz, d6-DMSO) □ ppm: 8.87 (1H, s), 7.86 (1H, s), 7.72 (1H, s), 5.18 (2H, s), 0.16 (9H, s). LCMS: rt=3.24 min.; m/z: 313.4 (M+Na)+, 291.2 (MH)+, 151.4 (100).
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[C:11](=[O:13])[CH3:12].[C:14](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH3:14][O:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[C:11](=[O:13])[CH3:12]
Reactant: CC(=O)c1c(C)cc(C)c(C)c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: COc1c(C)c(C)cc(C)c1C(C)=O
Temperature: 25 °C
Yield: 88.4 %

Procedure:
In acetone (30 mL) was dissolved 2.00 g (11.2 mmol) of 1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone which can be produced by the method disclosed in Chemical Research in Toxicology, 1997, vol. 10, No. 3, pp. 335-343, 3.10 g (22.4 mmol) of potassium carbonate, then 1.40 mL (22.5 mmol) of methyl iodide were added to the solution, and the resulting mixture was refluxed for 5 hours. After cooling to room temperature, the reaction mixture was concentrated, and the residue was poured into water, and extracted with ethyl acetate. The organic layers were combined, washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Wako gel C-100, hexane:ethyl acetate gradient) to obtain 1.90 g (9.90 mmol, Yield: 88.4%) of 1-(2-methoxy-3,4,6-trimethylphenyl)ethanone.
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[Cl:6][C:7]1[CH:8]=[C:9]([C:13](=[O:17])[CH:14](Br)[CH3:15])[CH:10]=[CH:11][CH:12]=1>>[CH3:15][CH:14]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[CH:8]=1)=[O:17]
Reactant: CC(Br)C(=O)c1cccc(Cl)c1
Reactant: CC(C)(C)N
Product: CC(NC(C)(C)C)C(=O)c1cccc(Cl)c1
Temperature: 25 °C

Procedure:
To 1 mole of m-chloroprophenone heated to 75±5° C., bromine was added dropwise under stirring, and the reaction temperature was kept at 75±5° C. during the addition and kept for 3 hours after the addition, m-chloro-α-bromopropiophenone (compound of formula (II)) was obtained. t-Butylamine was added to m-chloro-α-bromopropiophenone obtained above and the reaction mixture was refluxed for 5.5 hours. After excessive t-butylamine was evaporated below 100° C., the concentrated solution was cooled down to room temperature and then extracted with 1000 ml of toluene and 200 ml of water. The organic phase was dried with anhydrous magnesium sulfate (20 g) to obtain a solution of bupropion free base (compound III). HCl gas was bubbled into the solution of bupropion free base at room temperature until the PH value the reaction mixture was less than or equal to 4. After filtration, crude product of bupropion hydrochloride was obtained. The crude product of bupropion hydrochloride was dissolved in 1500 ml of ethyl acetate heated to 60° C., and decolorized with activated carbon (3 g) for 30 minutes and filtered. Then filtrate was cooled down, crystal bupropion hydrochloride crystallized. Wet product of bupropion hydrochloride was obtained after filtration and was dried in vacuum (−0.04˜−0.09 MPa, 60±5° C.) for 5 hours to obtain pure product. Total yields was 75% based on m-chloropropiophenone; HPLC's purify was over 99.9%.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][C:25]=1[CH3:33].C([O-])([O-])=O.[Na+].[Na+]>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>[CH3:33][C:25]1[CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=[CH:29][C:24]=1[C:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:13][CH:12]=1
Reactant: Cc1cc([N+](=O)[O-])ccc1Br
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: Cc1cc([N+](=O)[O-])ccc1C1=CCN(C(=O)OC(C)(C)C)CC1

Procedure:
A suspension of N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (0.29 g, 0.93 mmol), 1-bromo-2-methyl-4-nitrobenzene (0.20 g, 0.93 mmol), PdCl2(PPh3)2 (0.03 g, 0.05 mmol) and 3 M aqueous Na2CO3 (0.93 mL, 2.8 mmol) in 1,4-dioxane (10 mL) was degassed with nitrogen for 10 minutes then heated at reflux for 16 hours. The resulting mixture was concentrated under reduced pressure and purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound A38 (0.25 g, 83%); 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J=2.4 Hz, 1H), 8.03-7.98 (m, 1H), 7.22 (d, J=8.4 Hz, 1H), 5.63 (s, 1H), 4.09-4.04 (m, 2H), 3.64 (t, J=5.6 Hz, 2H), 2.38 (s, 3H), 2.35 (s, 2H), 1.51 (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C:12](=O)[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1.O.[C:23]1(C)C=CC=CC=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C:12](=[CH2:23])[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1
Reactant: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@H]12
Reactant: Cc1ccccc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: O
Solvent: CS(C)=O
Product: C=C1CC[C@@H]2[C@@H]3CCc4cc(OC)ccc4[C@H]3CC[C@]12C
Temperature: 65 °C

Procedure:
—Lithium amide (6.6 g) was added to a suspension of methyltriphenylphosphonium bromide (113 g) in dry toluene (300 ml) and dry dimethyl sulfoxide (24 ml). The reaction mixture was heated to 65° C. for 30 min. After cooling to 35-40° C., a solution of (14β)-3-methoxyestra-1,3,5(10)-trien-17-one [Johnson, W. S. et al, J. Am. Chem. Soc. 79, 2005 (1957); 30 g] in dry toluene (225 ml) was added and the mixture was heated at 60° C. for 22 h. Then it was cooled and poured into water. The product was extracted into ethyl acetate; the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. In order to achieve complete conversion of starting material, the procedure was repeated. The triphenylphosphine oxide was removed by addition of diethyl ether and filtration. Column chromatography of the crude product afforded (14β)-3-methoxy-17-methyleneestra-1,3,5(10)-triene (26 g).
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([C:7]2[S:11][C:10]([NH2:12])=[N:9][C:8]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:4][N:3]=1.[C:19](Cl)(=[O:21])[CH3:20]>>[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[S:11][C:10]([NH:12][C:19](=[O:21])[CH3:20])=[N:9][C:8]=2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:4][N:3]=1
Reactant: Cc1noc(-c2sc(N)nc2-c2ccccc2)n1
Reactant: CC(=O)Cl
Product: CC(=O)Nc1nc(-c2ccccc2)c(-c2nc(C)no2)s1

Procedure:
Prepared from 5-(3-methyl-[1,2,4]oxadiazol-5-yl)-4-phenyl-thiazol-2-ylamine and acetyl chloride.
Reaction SMILES: [C:1]([OH:10])(=O)[CH:2]([CH:4]([C:6](O)=[O:7])[OH:5])[OH:3].[CH3:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][NH2:29]>C1(C)C=CC=CC=1>[CH2:28]([N:29]1[C:6](=[O:7])[CH:4]([OH:5])[CH:2]([OH:3])[C:1]1=[O:10])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]/[CH:20]=[CH:19]\[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: CCCCCCCC/C=C\CCCCCCCCN
Reactant: O=C(O)C(O)C(O)C(=O)O
Solvent: Cc1ccccc1
Product: CCCCCCCC/C=C\CCCCCCCCN1C(=O)C(O)C(O)C1=O
Temperature: 100 °C
Reaction time: 1 h

Procedure:
150 Parts of tartaric acid (obtained from Sargent Welch) is added to 173 parts of toluene and the mixture is heated with stirring to 100° C. 281 parts of Armeen O (essentially oleylamine, a product of Armak Chemicals, Chicago, Ill.) is added slowly and in small portions while the system is kept under nitrogen purge. After the addition of the Armeen O is completed the contents are heated to 130° C. at which temperature the water formed is removed by azeotroping, and collected. The temperature is then raised to 160° C., after no more water is collected and kept at about 160° C. for one hour under nitrogen purge to remove the toluene. The liquid residue is then filtered through diatomaceous earth to yield the desired N-oleyltartarimide. Analysis shows nitrogen content of 3.42% and hydroxyl content of 8.33%. The tartarimide can be expressed as ##STR4##
Reaction SMILES: ClC(Cl)C.[CH3:5][O:6][C:7]1[CH:44]=[CH:43][C:10]([CH2:11][N:12]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:13]2[N:18]=[CH:17][C:16]([C:19]3[C:20]4[CH2:33][CH2:32][NH:31][C:21]=4[N:22]=[C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)[N:24]=3)=[CH:15][N:14]=2)=[CH:9][CH:8]=1.C(N(CC)CC)C.[CH2:52]([N:54]=[C:55]=[O:56])[CH3:53].[Cl-].[NH4+]>>[CH2:52]([NH:54][C:55]([N:31]1[C:21]2[N:22]=[C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:24]=[C:19]([C:16]3[CH:15]=[N:14][C:13]([N:12]([CH2:11][C:10]4[CH:9]=[CH:8][C:7]([O:6][CH3:5])=[CH:44][CH:43]=4)[CH2:34][C:35]4[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=4)=[N:18][CH:17]=3)[C:20]=2[CH2:33][CH2:32]1)=[O:56])[CH3:53]
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4)cn2)cc1
Reactant: CCN=C=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CC(Cl)Cl
Product: CCNC(=O)N1CCc2c(-c3cnc(N(Cc4ccc(OC)cc4)Cc4ccc(OC)cc4)nc3)nc(N3CCOCC3)nc21
Temperature: 25 °C
Yield: 97.5 %

Procedure:
To dichloroethane solution (2 ml) of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (100 mg, 0.185 mmol), triethylamine (780 μl, 5.56 mmol) and ethylisocyanate (780 μl, 5.56 mmol) were added, followed by refluxing for 6 hours. This was cooled to room temperature, followed by addition of saturated aqueous ammonium chloride solution, and passed through Whatman tube. The resulting organic layer was concentrated under reduced pressure, followed by purification by silica gel column chromatography (dichloromethane/methanol=100/1), to obtain 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid ethylamide (110.1 mg, Yield 97%). To this, trifluoroacetic acid (1 ml) and concentrated sulfuric acid (2 drops) were added, followed by stirring at 40° C. for 3 hours. After concentration of TFA under reduced pressure, water was added, followed by neutralization with 1M aqueous sodium hydroxide solution. The solid was filtered, followed by purification by silica gel column chromatography (dichloromethane/2M ammonia methanol=50/1), to obtain the desired compound as a yellow solid (20.9 mg, Yield 31%).
Reaction SMILES: [OH-].[Na+].C[C:4]([CH:6]1[CH:8]([CH2:9][C:10](Cl)([Cl:12])[Cl:11])[C:7]1([CH3:15])[CH3:14])=[O:5].BrBr.S([O-])([O-])=[O:19].[Na+].[Na+]>O.CO>[CH3:14][C:7]1([CH3:15])[CH:8]([CH:9]=[C:10]([Cl:12])[Cl:11])[CH:6]1[C:4]([OH:5])=[O:19]
Reactant: CC(=O)C1C(CC(Cl)(Cl)Cl)C1(C)C
Reactant: O=S([O-])[O-]
Agent: BrBr
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC1(C)C(C=C(Cl)Cl)C1C(=O)O
Temperature: 70 °C
Reaction time: 2 h
Yield: 67.5 %

Procedure:
To 250 ml of methanol solution containing 24 g of sodium hydroxide were added 17 g of 2,2-dimethyl-3-(2',2',2'-trichloroethyl)-cyclopropyl methyl ketone (purity: 97.9%, cis/trans ratio 91.5/8.5) under cooling with ice, and then 40 g of bromine were added dropwise at -10° C. to -5° C. for 20 minutes and after stirring the mixture at the same temperature for 2 hours, 25.2 g of sodium sulfite (7 hydrate) and 250 ml of water were added thereto, and the mixture was heated up to 70° C. and stirred for 47 hours with heating. Then the methanol was distilled off, water was added to the reaction mixture and neutral part was removed by extraction with ether. The water layer was acidified with conc. hydrochloric acid under cooling with ice. The deposited crystals were filtered, washed with water and dried to obtain 9.85 g of 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylic acid, cis/trans ratio 89.8/10.2, purity 91.8%, yield 72.9%.