Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:27]=[CH:26][C:11]2[C:12]3[C:13](=[CH:23][NH:24][CH:25]=3)[CH2:14][N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:10]=2[CH:9]=1.Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>CN(C)C=O.O>[CH2:33]([O:32][C:30](=[O:31])[CH2:29][N:24]1[CH:25]=[C:12]2[C:13]([CH2:14][N:15]=[C:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:10]3[CH:9]=[C:8]([Cl:7])[CH:27]=[CH:26][C:11]=32)=[CH:23]1)[CH3:34]
Reactant: CCOC(=O)CBr
Reactant: Clc1ccc2c(c1)C(c1ccccc1)=NCc1c[nH]cc1-2
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)Cn1cc2c(c1)-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Reaction time: 0.17 h

Procedure:
To a solution of 1.4 g (12.4 mmole) of potassium t-butoxide in 30 ml of dry dimethylformamide was added 2.4 g (8.2 mmole) of 8-chloro-6-phenyl-2H,4H-pyrrolo[3,4-d][2]benzazepine. The mixture was cooled to 0°, and stirred for 10 min. To the mixture was added 1.3 mol (11.7 mmole) of ethyl bromoacetate. The mixture was stirred at 0° for 45 min, diluted with water, and extracted with ether. The ether solution was washed with water, dried with sodium sulfate, and concentrated at reduced pressure to give a yellow oil. Purification by column chromatography (70 g SiO2, 9:1 methylene chloride/ether) gave as the first major component a yellow oil.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([NH:20][C@H:21]2[C@@H:25]([O:26][CH2:27][CH3:28])[CH2:24][N:23](C(OCC3C=CC=CC=3)=O)[CH2:22]2)=[N:5][C:6]([CH2:18][CH3:19])=[C:7]([C:9]2[C:10]([CH3:17])=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[N:8]=1)[CH3:2].C1CC=CCC=1>C(O)C.[Pd]>[CH2:27]([O:26][C@H:25]1[CH2:24][NH:23][CH2:22][C@H:21]1[NH:20][C:4]1[C:3]([CH2:1][CH3:2])=[N:8][C:7]([C:9]2[C:10]([CH3:17])=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[C:6]([CH2:18][CH3:19])[N:5]=1)[CH3:28]
Reactant: CCO[C@H]1CN(C(=O)OCc2ccccc2)C[C@H]1Nc1nc(CC)c(-c2ccc(OC)nc2C)nc1CC
Agent: [Pd]
Solvent: CCO
Solvent: C1=CCC=CC1
Product: CCO[C@H]1CNC[C@H]1Nc1nc(CC)c(-c2ccc(OC)nc2C)nc1CC
Reaction time: 2 h
Yield: 86.9 %

Procedure:
To a solution of benzyl (3R,4S)-3-{[3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate (1.35 g) in ethanol (26 ml) was added 1,4 cyclohexadiene (2.45 ml, 10 eq.) and 10% Pd/C (1.5 g). The reaction mixture stirred 2 h, was filtered through celite and concentrated. Purification via MPLC chromatography eluting with 2–6% methanol/CH2Cl2 with 0.5% ammonium hydroxide afforded the title compound as an amber oil (870 mg, 87%): 1H NMR (400 MHz, CDCl3) δ) 7.41, 6.64, 5.34–5.32, 4.52, 4.05, 3.97, 3.68, 3.53, 3.43, 3.22, 3.15, 2.92, 2.70, 2.46, 2.29, 1.32–1.25, 1.14; IR (liq.) 2972, 2935, 2408 (w), 2238 (w), 2019 (w), 1971 (w), 1596, 1563 (s), 1499, 1474 (s), 1426, 1394, 1304 (s), 1251, 1042 cm−1 HRMS (ESI) calcd for C21H31N5O2+H1 386.2556. found 386.2544.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>N1C=CC=CC=1>[N:11]1([C:2]2[CH:7]=[C:6]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:4][N:3]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1
Reactant: C1CNCCN1
Reactant: CC(=O)c1ccnc(Cl)c1
Solvent: c1ccncc1
Product: CC(=O)c1ccnc(N2CCNCC2)c1
Yield: 21 %

Procedure:
1-(2-Chloro-4-pyridyl)ethanone (156 mg, 1 mmol), piperazine (861 mg, 10 mmol) and pyridine (5 ml) were placed in a Radley vial and heated at reflux overnight. The mixture was concentrated under reduced pressure to dryness, the residue was mixed with toluene and evaporated under reduced pressure to remove excess of piperazine. The last step was repeated several times. The residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 51 mg of a solid (0.21 mmol, yield 21%) MS (multi-mode) m/z=206.2 [M+1]+.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[C:13]3[C:8]=2[CH:9]=[CH:10][CH:11]=[N:12]3)[CH2:3][CH2:2]1.Cl.C(=O)([O-])[O-].[K+].[K+]>O>[NH2:17][C:14]1[CH:15]=[CH:16][C:7]([N:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[CH:9]2
Reactant: O=[N+]([O-])c1ccc(N2CCOCC2)c2cccnc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Nc1ccc(N2CCOCC2)c2cccnc12
Reaction time: 1 h
Yield: 53 %

Procedure:
5-Morpholino-8-nitroquinoline, 3.90 g, was dissolved into 30 ml of water and 30 ml of hydrochloric acid. To this mixture 10.2 g of stannous chloride.dihydrate was added and the mixture was heated on a water bath under stirring for 1 hour. After cooling, the mixture was neutralized with potassium carbonate and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. Ethyl acetate was evaporated to produce 1.83 g (yield: 53%) of 8-amino-5-morpholinoquinoline. This compound was dissolved into 10 ml of water and 6 ml of concentrated HCl, and to the solution an aqueous solution containing 0.62 g of sodium nitrite was added dropwise while stirring at -15° C. The diazonium salt thus obtained was neutralized with sodium bicarbonate, and resulting product was added at 0° C. into an aqueous solution of cuprous cyanide (prepared from 2.0 g of cuprous chloride and 3.4 g of potassium cyanide). The mixture was stirred at the same temperature for 1 hour, then at 70° C. for 30 minutes to complete the reaction. The reaction mixture was extracted with ethyl acetate and the extract was dried over anhydrous sodium sulfate. Ethyl acetate was evaporated and the residue was refined by column chromatography on silica gel using a chloroform-n-hexane (3:2) mixed solvent as an eluent. The crystals thus obtained were recrystallized from ethanol to yield 0.12 g (yield: 6.2%) of 5-morpholino-8-quinolinecarbonitrile (Compound No. 13)
Reaction SMILES: O1CCCC1.[Br:6][C:7]1[C:8]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[N:9][C:10]([S:13][CH3:14])=[N:11][CH:12]=1.N1(C2CCCCCCCCCC2)CCCCCCCCCN1.[C:44]([CH2:46][C:47](OCC)=[O:48])#[N:45]>O>[Br:6][C:7]1[C:8]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:47](=[O:48])[CH2:46][C:44]#[N:45])[CH2:17]2)=[N:9][C:10]([S:13][CH3:14])=[N:11][CH:12]=1
Reactant: CSc1ncc(Br)c(N[C@H]2CCCNC2)n1
Reactant: CCOC(=O)CC#N
Agent: C1CCCCCC(N2CCCCCCCCCN2)CCCC1
Solvent: O
Solvent: C1CCOC1
Product: CSc1ncc(Br)c(N[C@H]2CCCN(C(=O)CC#N)C2)n1

Procedure:
A tetrahydrofuran solution (6 ml) of (5-bromo-2-methylsulfanyl-pyrimidin-4-yl)-(S)-piperidin-3-yl-amine (from Example 76, step 1 above) (300 mg, 0.99 mmol), diazabicycloundecane (530 mg, 3.5 mmol) and ethyl 2-cyanoacetate was stirred at room temperature for 20 hours. The reaction was diluted with water and extracted with ethyl acetate (2×). The organics were dried and evaporated to give 3-[(S)-3-(5-bromo-2-methylsulfanyl-pyrimidin-4-ylamino)-piperidin-1-yl]-3-oxo-propionitrile as an oil. MS (ES+): 371.
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[F:52][C:53]1[CH:58]=[CH:57][C:56]([NH:59][CH:60]2[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)=[C:55]([C:66]([F:69])([F:68])[F:67])[CH:54]=1>CN(C=O)C.O>[F:52][C:53]1[CH:58]=[CH:57][C:56]([NH:59][CH:60]2[CH2:61][CH2:62][N:63]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]3[CH:17]=[C:16]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:20][N:19]=3)=[O:22])[CH2:64][CH2:65]2)=[C:55]([C:66]([F:69])([F:67])[F:68])[CH:54]=1
Reactant: Fc1ccc(NC2CCNCC2)c(C(F)(F)F)c1
Reactant: O=C(O)CNC(=O)c1cc(-c2ccccc2)[nH]n1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC(=O)N1CCC(Nc2ccc(F)cc2C(F)(F)F)CC1)c1cc(-c2ccccc2)[nH]n1
Reaction time: 8 h
Yield: 36 %

Procedure:
DIPEA (232 mg, 1.8 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (140 mg, 0.6 mmol) in DMF (2 mL) followed by HOBt (97 mg, 0.7 mmol) and EDCI.HCl (137 mg, 0.7 mmol). After 2 minutes (4-fluoro-2-trifluoromethyl-phenyl)-piperidin-4-yl-amine dihydrochloride (prepared according to the method used for the synthesis of Intermediate 3) (150 mg, 0.6 mmol) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate and dried over sodium sulfate. The organic layer was concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) to afford 105 mg (36% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(4-fluoro-2-trifluoromethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 490.18, 95.36%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.0 (t, 1H), 7.8 (m, 2H), 7.4 (m, 6H), 7.1 (m, 2H), 4.6 (d, 1H), 4.4 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (m, 2H), 1.5 (m, 2H), 1.4 (m, 1H).
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(=O)([O-])[O-].[K+].[K+].[C:13]1([C:19]2[C:20](=[O:30])[NH:21][C:22](=[O:29])[N:23]3[CH2:28][CH2:27][CH2:26][S:25][C:24]=23)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C>[CH2:2]([N:21]1[C:20](=[O:30])[C:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:24]2[S:25][CH2:26][CH2:27][CH2:28][N:23]2[C:22]1=[O:29])[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=c1[nH]c(=O)n2c(c1-c1ccccc1)SCCC2
Reactant: CCCCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCn1c(=O)c(-c2ccccc2)c2n(c1=O)CCCS2
Yield: 64.6 %

Procedure:
1-Iodopentane (2.29 g), potassium carbonate (1.28 g) and 9-phenyl-3,4-dihydro-2H,6H-pyrimido[6,1-b][1,3]thiazine-6,8(7H)-dione (2 g) in DMF (30 ml) were stirred at 100° C. for 15 hours. The reaction solution was concentrated to dryness, and the residue was purified by column chromatography on silica gel. The obtained crude crystals were recrystalized from ethyl acetate-hexane to give colorless crystals (1.64 g, 65%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]2)=[C:4]([CH3:20])[CH:3]=1.[C:21](O)(=O)C.C=O.O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH3:21])[CH:9]2[CH2:10][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:12]2)=[C:4]([CH3:20])[CH:3]=1
Reactant: Cc1cc(F)ccc1NC1CN(C(=O)OC(C)(C)C)C1
Reactant: CC(=O)O
Agent: C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Solvent: ClCCCl
Solvent: O
Product: Cc1cc(F)ccc1N(C)C1CN(C(=O)OC(C)(C)C)C1
Yield: 67.5 %

Procedure:
A solution of tert-butyl 3-((4-fluoro-2-methylphenyl)amino)azetidine-1-carboxylate (D30) (240 mg, 0.856 mmol), acetic acid (0.49 ml, 8.56 mmol), Formaldehyde 36% wt. in water (0.066 ml, 0.856 mmol) and sodium(triacetoxy)borohydride (725 mg, 3.424 mmol) in 1,2-dichloroethane (7 ml) was stirred under N2 atmosphere at room temperature for 1 day. NaHCO3 sat. solution (25 ml) was added. After phase separation, the aqueous layer was extracted with dichloromethane (2×35 ml). The organics after solvent evaporation were purified by Biotage SNAP-Si cartridge (10 g) eluting with cyclohexane/ethylacetate from 90/10 up to 80/20. Collected fractions after solvent evaporation afforded the title compound (D33) (170 mg)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:17][OH:18])[CH:5]=[C:6]([F:16])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=1.Cl[C:20]1[CH:21]=[C:22]2[N:29](C(OC(C)(C)C)=O)[C:28]([CH3:38])([CH3:37])[CH2:27][N:23]2[C:24](=[O:26])[N:25]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([F:16])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=1)[CH2:17][O:18][C:20]1[CH:21]=[C:22]2[NH:29][C:28]([CH3:38])([CH3:37])[CH2:27][N:23]2[C:24](=[O:26])[N:25]=1
Reactant: OCc1cc(F)c(Oc2ccnc(F)c2)c(F)c1
Reactant: CC(C)(C)OC(=O)N1c2cc(Cl)nc(=O)n2CC1(C)C
Product: CC1(C)Cn2c(cc(OCc3cc(F)c(Oc4ccnc(F)c4)c(F)c3)nc2=O)N1

Procedure:
The title compound was prepared by a procedure similar to that described for E9 starting from (3,5-difluoro-4-((2-fluoropyridin-4-yl)oxy)phenyl)methanol and tert-butyl 7-chloro-2,2-dimethyl-5-oxo-2,3-dihydroimidazo[1,2-c]pyrimidine-1(5H)-carboxylate.
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:13]=1[C:14]([OH:16])=O)/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])\[CH3:4].[NH2:23][CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][N:26]1[CH2:30][CH3:31]>>[CH2:30]([N:26]1[CH2:27][CH2:28][CH2:29][CH:25]1[CH2:24][NH:23][C:14](=[O:16])[C:13]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:12]=1[O:11][CH2:1]/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])\[CH3:4])[CH3:31]
Reactant: COc1ccc(OC/C=C(\C)CCC=C(C)C)c(C(=O)O)c1
Reactant: CCN1CCCC1CN
Product: CCN1CCCC1CNC(=O)c1cc(OC)ccc1OC/C=C(\C)CCC=C(C)C
Yield: 86 %

Procedure:
In a manner identical to Example 15, 2-geranyloxy-5-methoxybenzoic acid(1.52 g) was subjected to a condensation reaction with 2-aminomethyl-1-ethylpyrrolidine (0.7 ml), thereby yielding 1.78 g(86%) of the aimed compound.
Reaction SMILES: [C:1]([O:9][CH:10]1[CH2:13][C:12](=[O:14])[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([Mg]Br)#[CH:16]>O1CCCC1>[C:1]([O:9][CH:10]1[CH2:13][C:12]([C:15]#[CH:16])([OH:14])[CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CC(OC(=O)c2ccccc2)C1
Reactant: C#C[Mg]Br
Solvent: C1CCOC1
Product: C#CC1(O)CC(OC(=O)c2ccccc2)C1
Temperature: -76 °C
Reaction time: 0.5 h

Procedure:
This compound was prepared according to a procedure similar to that described in Procedure A. Into a 25-mL three neck-round bottle flask, was placed a solution of 3-oxocyclobutyl benzoate (380 mg, 2.0 mmol, 1.00 equiv) in tetrahydrofuran (10 mL). Ethynylmagnesium bromide (0.5 M in tetrahydrofuran, 6 mL) was added dropwise, then resulting solution was stirred for 30 min at −76° C. When the mixture was warmed to room temperature in air, quenched by addition of saturated aqueous ammonium chloride (5 mL), the organic layer was washed by brine (10 mL), dried and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:6). This resulted in 300 mg (69%) of 3-ethynyl-3-hydroxycyclobutyl benzoate as a white solid. 1H-NMR: (300 MHz, CDCl3, ppm) δ 8.100-8.000 (m, 1H), 7.610-7.500 (t, 1H), 7.499-7.380 (m, 2H), 5.160-5.040 (m, 1H), 3.150-3.010 (m, 2H), 2.610-2.470 (m, 3H).
Reaction SMILES: C([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C@@H:14]([O:23]C(=O)C)[C@@H:13]([OH:27])[C@H:12]4[OH:28])[CH2:9][CH2:8][C:7]=2[CH:6]=1)(=O)C.C(OC1C=CC2[C@@H]3[C@H]([C@H]4[C@@](CC3)(C)[C@H](OC(=O)C)[C@H](O)[C@@H]4O)CCC=2C=1)(=O)C>CO>[CH3:16][C@@:15]12[C@@H:14]([OH:23])[C@H:13]([OH:27])[C@H:12]([OH:28])[C@H:11]1[C@@H:10]1[CH2:9][CH2:8][C:7]3[CH:6]=[C:5]([OH:4])[CH:22]=[CH:21][C:20]=3[C@H:19]1[CH2:18][CH2:17]2
Reactant: CC(=O)Oc1ccc2c(c1)CC[C@H]1[C@@H]3[C@H](O)[C@H](O)[C@H](OC(C)=O)[C@@]3(C)CC[C@H]21
Agent: CC(=O)Oc1ccc2c(c1)CC[C@H]1[C@@H]3[C@@H](O)[C@@H](O)[C@@H](OC(C)=O)[C@@]3(C)CC[C@H]21
Solvent: CO
Product: C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1[C@@H](O)[C@@H](O)[C@@H]2O

Procedure:
The carbonyl group at C17 of the 3-hydroxyestetra-1,3,5(10),15-tetraen-17-one was reduced with LiAlH4 to estra-1,3,5(10),15-tetraene-3,17-diol that was isolated as the diacetate (compound B). Compound B was subjected to cis-hydroxylation of the double bond of D ring by using Osmium tetraoxyde which resulted into the formation of estra-1,3,5(10)-triene-3,15α,16α,17α-tetraol-3,17-diacetate (compound C) as the major product associated with estra-1,3,5(10)-triene-3,15β,16β,17β-tetrol-3,17 diacetate. These compounds were isolated by thin layer chromatography. Compound C under heating with K2 CO3 in methanol produces estetrol (compound D) (Scheme 1). The overall yield of this three step process was, starting from estrone 3-hydroxyestetra-1,3,5(10),15-tetraen-17-one, only about 7%.
Reaction SMILES: Br[C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([C@H:18]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:19]([O:21][CH3:22])=[O:20])[C:8]([CH3:28])=[CH:7][C:5]=2[N:6]=1.[Cl-].[Li+].[Cl:31][C:32]1[N:37]=[C:36]([Sn](CCCC)(CCCC)CCCC)[CH:35]=[CH:34][N:33]=1>O1CCOCC1.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.[Cu]I>[C:24]([O:23][C@@H:18]([C:9]1[C:8]([CH3:28])=[CH:7][C:5]2[N:6]=[C:2]([C:34]3[CH:35]=[CH:36][N:37]=[C:32]([Cl:31])[N:33]=3)[S:3][C:4]=2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:19]([O:21][CH3:22])=[O:20])([CH3:27])([CH3:26])[CH3:25]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnc(Cl)n1
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(Br)sc2c1-c1ccc(Cl)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Solvent: C1COCCO1
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(Cl)n3)sc2c1-c1ccc(Cl)cc1
Temperature: 90 °C

Procedure:
A microwave vial was charged with (S)-methyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (496.3 mg, 1.03 mmol), tetrakis(triphenylphosphine)palladium(0) (178.2 mg, 0.15 mmol), lithium chloride (43.6 mg, 1.03 mmol), and copper(I) iodide (58.7 mg, 0.31 mmol) and the vial was evacuated and backfilled with argon (3×). To this mixture was added 2-chloro-4-(tributyl)stannyl pyrimidine (456.3 mg, 1.13 mmol) in 1,4-dioxane (10 mL). The reaction mixture was heated at 90° C. overnight, then cooled, filtered through Celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. LCMS-ESI+ calc'd for C25H23Cl2N3O3S (M+H+): 516.1; Found: 516.2 (M+H+).
Reaction SMILES: [CH3:1][CH:2]([O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[O:11])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH2:19]([O:27][C:28]([O:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=1)=[O:29])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].O.C1(C)C=CC=CC=1>N1C=CC=CC=1>[CH3:1][CH:2]([O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:35](=[O:36])[C:34]2[CH:38]=[CH:39][C:31]([O:30][C:28]([O:27][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:29])=[CH:32][CH:33]=2)=[CH:14][CH:13]=1)=[O:11])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCOC(=O)Oc1ccc(C(=O)Cl)cc1
Reactant: CCCCCCC(C)OC(=O)c1ccc(O)cc1
Solvent: O
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCCCCCCCOC(=O)Oc1ccc(C(=O)Oc2ccc(C(=O)OC(C)CCCCCC)cc2)cc1
Reaction time: 2 h
Yield: 28.2 %

Procedure:
Optically active 4-(1-methylheptyloxycarbonyl)phenol (10 g, 0.04 mol) was dissolved in pyridine (70 ml), followed by dropwise adding to the solution, under cooling, 4-octyloxycarbonyloxybenzoic chloride (11.4 g, 0.035 mol) prepared in the same manner as in the paragraph (ii) of Example 1, agitating the mixture at 50°-60° C. for 2 hours, placing water and toluene in the reaction solution after completion of the reaction, sufficiently agitating the mixture, washing the separated toluene layer with 6N--HCl, then with 2N-NaOH aqueous solution, further with water until the washing water became neutral, drying the resulting toluene layer with anhydrous sodium sulfate, distilling off toluene to obtain a raw objective product, and recrystallizing this product from ethanol to obtain optically active 4-octyloxycarbonyloxybenzoic acid 4-(1-methylheptyloxycarbonyl)phenyl ester (5.2 g), which exhibited no liquid crystal phase and had a m.p. of 33.0° C. Further, by replacing octyl chloroformate used, by other alkyl chloroformates, various optically active 4-alkyloxycarbonyloxybenzoic acid 4-(1-methyl-heptyloxycarbonyl)phenyl esters are obtained. The phase transition points thereof are shown in Tables 1 and 2.
Reaction SMILES: [CH2:1]([O:3][C:4]([O:6][C@@H:7]1[C@@:32]2([CH3:33])[C:11](=[CH:12][CH2:13][C@@H:14]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:34])[C@H:15]3[CH2:16][CH2:17][C@@H:18]2[C@H:19]([CH3:27])[CH2:20][CH2:21][CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])[CH2:10][C@@H:9]([O:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:8]1)=[O:5])[CH3:2].BrN1C(C)(C)C(=O)N(Br)C1=O.CC1C=C(C)N=C(C)C=1>CCCCCC.C1(C)C(C)=CC=CC=1.C(OC(=O)C)C>[CH2:1]([O:3][C:4]([O:6][C@@H:7]1[C@@:32]2([CH3:33])[C:11](=[CH:12][CH:13]=[C:14]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:34])[C@H:15]3[CH2:16][CH2:17][C@@H:18]2[C@H:19]([CH3:27])[CH2:20][CH2:21][CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])[CH2:10][C@@H:9]([O:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:8]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)O[C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OCC)C1
Agent: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1C
Solvent: CCCCCC
Product: CCOC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H]([C@H](C)CCCC(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OCC)C1
Temperature: 95 °C
Reaction time: 0.33 h
Yield: 86.1 %

Procedure:
To a solution of 1α,3β-diethoxycarbonyloxy-25-hydroxycholesta-5-ene (562 mg, 1 m mole) in dry hexane (10 m), 1,3-dibromo-5,5-dimethylhydantoin (172 mg, 0.6 m moles) was added dropwise under stirring and heating at oil bath temperature of 95° C., and the mixture was continued to react under the irradiation of infrared rays for 15 minutes. The reaction mixture was cooled, and the resulting precipitate was removed by filtration, the filtrate was concentrated at reduced pressure at 40° C. to afford a residual product. Xylene was added to this substance to form a solution. The resulting solution was added dropwise to a solution held at 170° C. of s-collidine (2.5 ml) in dry xylene (3 ml), and the reaction was carried out for additional 20 minutes. After the reaction, the resulting precipitate was removed by filtration and the filtrate was concentrated under reduced pressure at 40° C. to give residual product. The product was dissolved in ethylacetate (20 ml). The ethylacetate solution was washed with 1 N hydrochloric acid (3×10 ml), saturated sodium bicarbonate and water, and dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give 482 mg of residual product.