Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[C@H:2]([C:10]([NH:12][C@H:13]([C:23]([NH:25][C@H:26]([C:28](O)=[O:29])[CH3:27])=[O:24])[CH2:14][O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:41][C@H:42]([C:47]([CH2:49][Cl:50])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45].Cl.N(C(OCC1C=CC=CC=1)=O)[C@H](C(NCC(N[C@H](C(N[C@H](C(CCl)=O)CC(C)C)=O)CC(C)C)=O)=O)CC1C=CC=CC=1>>[NH:1]([C:31]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:32])[C@H:2]([C:10]([NH:12][C@H:13]([C:23]([NH:25][C@H:26]([C:28]([NH:41][C@H:42]([C:47]([CH2:49][Cl:50])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:29])[CH3:27])=[O:24])[CH2:14][O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(C)C[C@H](N)C(=O)CCl
Reactant: C[C@H](NC(=O)[C@H](COCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)O
Agent: CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)CCl
Agent: Cl
Product: CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](COCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)CCl

Procedure:
Z-Phe-Ser(OCH2C6H5)-Ala-LeuCH2Cl was prepared by coupling Z-Phe-Ser(OCH2C6H5)-Ala-OH (1.37 g, 2.5 mmol) to H-LeuCH2Cl.HCl by a mixed anhydride coupling procedure substantially similar to that used for the preparation of Z-Phe-Gly-Leu-LeuCH2Cl in Procedure C, above. Product was obtained as a crystalline solid, 0.98 g (m.p. 167°-168°). Anal: Calcd. for C37H45N4O7 : C, 64.09; H, 6.56; N, 8.08; Found: C, 64.22; H, 6.38; N, 8.08.
Reaction SMILES: [Br:1][C:2]1[C:3]([S:11][C:12]2[NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[C:15]=3[N:21]=2)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.CC1C=CC(S(O[CH2:33][CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([CH:41]=[O:42])[CH2:37][CH2:36]2)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[NH2:20][C:16]1[C:15]2[N:21]=[C:12]([S:11][C:3]3[C:2]([Br:1])=[CH:10][C:6]4[O:7][CH2:8][O:9][C:5]=4[CH:4]=3)[N:13]([CH2:33][CH2:34][CH:35]3[CH2:40][CH2:39][N:38]([CH:41]=[O:42])[CH2:37][CH2:36]3)[C:14]=2[CH:19]=[CH:18][N:17]=1
Reactant: Nc1nccc2[nH]c(Sc3cc4c(cc3Br)OCO4)nc12
Reactant: Cc1ccc(S(=O)(=O)OCCC2CCN(C=O)CC2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1nccc2c1nc(Sc1cc3c(cc1Br)OCO3)n2CCC1CCN(C=O)CC1
Temperature: 25 °C
Yield: 42.1 %

Procedure:
To a solution of 2-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-1H-imidazo[4,5-c]pyridin-4-amine (175 mg, 0.480 mmol), 2-(1-formylpiperidin-4-yl)ethyl 4-methylbenzenesulfonate (194 mg, 0.624 mmol), and Cs2CO3 (267 mg, 0.816 mmol) in DMF (3.0 mL) was heated at 85° C. for 10 h. After cooling to RT, the mixture was diluted with water, extracted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuum. The residue was triturated with EtOAc, filtered, and dried to give the title compound (102 mg, 42%): 1H NMR (DMSO-d6) δ 7.94 (s, 1H), 7.72 (d, J=6.0 Hz, 2H), 7.39 (s, 1H), 6.79 (d, J=6.0 Hz, 2H), 6.66 (s, 1H), 6.41 (s, 2H), 6.07 (s, 2H), 4.20 (t, J=6.8 Hz, 2H), 4.10 (brd, J=13.6 Hz, 1H), 3.62 (brd, J=13.2 Hz, 1H), 2.91 (td, J=12.0, 2.4 Hz, 1H), 2.54 (m, 1H), 1.70 (t, J=6.8 Hz, 2H), 1.57-1.42 (m, 3H), 1.03 (m, 1H), 0.94 (m, 1H); LC/MS [M+H]+ 504.07.
Reaction SMILES: [F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:13](Cl)(=O)[C:14](Cl)=O.C(O)C>ClCCl.CN(C)C=O>[CH2:13]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([F:12])=[C:10]([F:11])[C:2]=1[F:1])[CH3:14]
Reactant: O=C(O)c1ccc(F)c(F)c1F
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)c1ccc(F)c(F)c1F
Reaction time: 0.75 h
Yield: 97.3 %

Procedure:
To a solution of 2,3,4-trifluorobenzoic acid (10.85 g, 61.6 mmol) in dichloromethane (100 mL) is added oxalyl chloride (13.5 mL, 154 mmol) and N,N-dimethylformamide (3 drops). After 45 minutes, the reaction mixture is concentrated under vacuum. The resulting residue is dissolved in dichloromethane (100 mL) and to this solution is added ethanol (18 mL, 310 mmol). After 30 minutes, the reaction mixture is diluted with dichloromethane and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated to afford the title compound as an oil (12.23 g). 1H NMR (CDCl3): δ 7.93-7.67 (m, 1H), 7.09-6.96 (m, 1H), 4.39 (q, 2H), 1.40 (t, 3H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][NH:18]C(OCC1C=CC=CC=1)=O)=[CH:5]2.[Si](I)(C)(C)C.[NH:49]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][C:51](O)=[O:52].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC#N.CN(C=O)C.CO>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][NH:18][C:51](=[O:52])[CH2:50][NH:49][C:54]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:55])=[CH:5]2
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: CN(C(=O)NCc1cccc(F)c1Cl)[C@@H](CNC(=O)OCc1ccccc1)COC(=O)Nc1cc2cc(F)ccc2cn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: C[Si](C)(C)I
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: CN(C)C=O
Solvent: CC#N
Product: CN(C(=O)NCc1cccc(F)c1Cl)[C@@H](CNC(=O)CNC(=O)OC(C)(C)C)COC(=O)Nc1cc2cc(F)ccc2cn1
Reaction time: 0.25 h
Yield: 70.6 %

Procedure:
To a solution of (S)-3-benzyloxycarbonylamino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl 6-fluoroisoquinolin-3-ylcarbamate (1.3 g, 2.13 mmol) in CH3CN (20.0 mL) was added TMSI (0.35 mL, 2.56 mmol). The mixture was stirred for 15 min. MeOH (20.0 mL) was added and stirring continued another 15 min. The mixture was concentrated and partitioned between diethyl ether (30 mL) and HCl (2 N, 20 mL). The aqueous layer was separated, adjusted to pH 9, extracted with EtOAc (200 mL×2). The combined organic layers were washed brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give an crude oil, which was dissolved in DMF (6.0 mL). To this DMF solution were added Boc-Gly-OH (0.36 g, 2.03 mmol) and HBTU (0.77 g, 2.03 mmol). The mixture was stirred for 1 h. The crude was filtered and purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-3-(2-tert-butoxycarbonylaminoacetamido)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl 6-fluoroisoquinolin-3-ylcarbamate (0.91 g, 78%). LRMS (M+H+) m/z 635.2.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=2)=[CH:2]1.[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][Br:13])=[CH:8][CH:7]=2)=[CH:2]1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(-c2ccsc2)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1ccc(-c2ccsc2)cc1

Procedure:
To a solution of 4-(3-thienyl)toluene (3.56 g, 20.5 mmol) in carbon tetrachloride (100 ml) is added N-bromosuccinimide (3.64 g, 20.5 mol) and benzoyl peroxide (80 mg, 3.3 mmol). The reaction mixture is heated at reflux for 24 hrs. and concentrated in vacuo. The reaction mixture is recrystallized from ethanol to afford 4-(3-thienyl)benzyl bromide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH:20]=O.[F:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25][NH2:26].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH2:20][NH:26][CH2:25][C:24]1[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=1[F:22]
Reactant: O=Cc1nc2ccc(F)cc2c(=O)n1-c1ccccc1Cl
Reactant: NCc1ccccc1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: O=c1c2cc(F)ccc2nc(CNCc2ccccc2F)n1-c1ccccc1Cl
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.20 g, 0.66 mmol), 2-fluorobenzylamine (0.038 mL, 0.33 mmol), and acetic acid (0.19 mL, 3.3 mmol) in dichloroethane (10 mL) was chilled to 0° C. and sodium triacetoxyborohydride (0.350 g, 1.65 mmol) was added. The reaction was stirred for 1 hour at 0° C. and then allowed to warm to ambient temperature and stirred 16 hours. The reaction was quenched by addition of saturated aqueous bicarbonate and continued stirring for 30 minutes. The phases were separated and the aqueous layer was extracted with methylene chloride. The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (30 g) with elution proceeding as follows: 30% ethyl acetate/hexane (100 mL), nil; (50 mL), unweighed impurity; (100 mL), nil; (125 mL), unweighed impurity; (150 mL), unweighed 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-methanol; (450 mL), unweighed 3-(2-chloro-phenyl)-6-fluoro-2-[(2-fluoro-benzylamino)-methyl]-3H-quinazolin-4-one as a pale pink solid which had: mp 140° C.; 1H NMR δ 7.89 (dd, J=3, 8 Hz, 1 H), 7.76 (dd, J=4, 9 Hz, 1 H), 7.58 (dd, J=2, 8 Hz, 1 H), 7.53-7.41 (m, 4 H), 7.35-7.30 (m, 2 H), 7.07 (t, J=8 Hz, 1 H), 6.99 (t, J=10 Hz, 1 H), 3.89 (ABq, Δv1-3=21 Hz, J=13 Hz, 2 H), 3.46 (ABq, Δv1-3=31 Hz, J=17 Hz, 2 H); APCI MS m/z=412 (P−1).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[F:13])[S:9][C:8]([CH3:15])([CH3:14])[CH2:7][C:6]2=[O:16])#[CH:2].I[C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=1>CCN(CC)CC.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.[Cu]I>[CH3:15][C:8]1([CH3:14])[CH2:7][C:6](=[O:16])[C:5]2[C:10](=[CH:11][C:12]([F:13])=[C:3]([CH2:1][CH2:2][C:18]3[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=3)[CH:4]=2)[S:9]1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: C#Cc1cc2c(cc1F)SC(C)(C)CC2=O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(CCc2cc3c(cc2F)SC(C)(C)CC3=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.9 %

Procedure:
A solution of 6-ethynyl-7-fluoro-2,2-dimethylthiochroman-4-one (Compound 207, 330.0 mg, 1.41 mmol) and ethyl 4-iodobenzoate (392 mg, 1.41 mmol) in 10.0 mL Et3N was purged with argon for 15 minutes. To this solution was added bis(triphenylphosphine)-palladium(II) chloride (247 mg, 0.35 mmol) and copper(I) iodide (67.0 mg, 0.35 mmol). After sparging for an additional 10 minutes with argon, the solution was stirred overnight at room temperature. The reaction mixture was diluted with EtOAc and filtered through a pad of Celite using an EtOAc wash. Concentration of the filtrate under reduced pressure, followed by column chromatography (3 to 5% EtOAc/hexanes) of the residual solid afforded 490.0 mg (91%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCl3)δ: 8.31 (1H, d, J=7.6 Hz), 8.04 (2H, d, J=8.3 Hz), 7.60 (2H, d, J=8.3 Hz), 7.00 (1H, d, J=9.3 Hz), 4.40 (2H, q, J=7.1 Hz), 2.89 (2H, s), 1.50 (6H, s), 1.41 (3H, t, J=7.1 Hz).
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:11]3[CH2:19][CH2:18][NH:17][CH2:16][C:12]=3[N:13]=[CH:14][N:15]=2)=[CH:5][CH:4]=1.[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C(N(CC)CC)C>C1COCC1.CC([O-])=O.CC([O-])=O.[Cu+2]>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[C:11]3[CH2:19][CH2:18][N:17]([C:24]4[CH:23]=[C:22]([CH3:31])[CH:27]=[CH:26][CH:25]=4)[CH2:16][C:12]=3[N:13]=[CH:14][N:15]=2)=[CH:7][CH:8]=1
Reactant: FC(F)(F)c1ccc(Nc2ncnc3c2CCNC3)cc1
Reactant: Cc1cccc(B(O)O)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1cccc(N2CCc3c(ncnc3Nc3ccc(C(F)(F)F)cc3)C2)c1
Reaction time: 6 h
Yield: 4.7 %

Procedure:
N-(4-(Trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine (100 mg, 0.34 mmol) was dissolved in anhydrous THF (2 mL). To the mixture was added m-tolylboronic acid (92 mg, 0.68 mmol), Cu(OAc)2 (124 mg, 0.68 mmol) and triethylamine (0.68 g, 0.095 mL). The mixture was agitated for 6 h and the solvent was removed under a vacuum. The residue was purified using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as reddish powder (6.2 mg, 5%).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[N:5][N:6]=1.[C:7]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1)(=[O:9])[CH3:8]>N1C=CC=CC=1.Cl>[S:3]1[CH:4]=[N:5][N:6]=[C:2]1[NH:1][S:17]([C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:7](=[O:9])[CH3:8])=[CH:16][CH:15]=1)(=[O:19])=[O:18]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1nncs1
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc(S(=O)(=O)Nc2nncs2)cc1
Temperature: 95 °C
Yield: 94.9 %

Procedure:
2-Amino-1,3,4-thiadiazole (500 mg, 4.95 mmol) was suspended in pyridine (1.26 mL). p-Acetamidobenzenesulfonyl chloride (1.2 g, 5.15 mmol) was added and the mixture was heated to 95° C. for 1 h. The mixture was dissolved in 10% aqueous HCl and extracted with ethyl acetate. The organic extracts were washed with water and dried over anhydrous Na2SO4. Evaporation of the solvent yielded the crude product (1.4 g, 4.7 mmol, 95%). Recrystallization from CH2Cl2/MeOH gave pure product, mp 216-217° C. (lit1 mp 214-215° C.); 1H NMR (250 MHz, CDCl3) δ 2.07 (3, s), 7.73 (4, s), 8.74 (1, s), 10.35 (1, s), 14.35 (1, br s); 13C NMR (62.5 MHz, DMSO) δ 24.2, 118.7, 127.0, 135.6, 143.0, 144.9, 167.2, 169.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[CH3:12])[CH3:2].[Se](=O)=[O:14]>>[CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[CH:12]=[O:14])[CH3:2]
Reactant: CCn1c(C)nc2ccccc21
Reactant: O=[Se]=O
Product: CCn1c(C=O)nc2ccccc21
Yield: 52 %

Procedure:
Oxidation of the 1-ethyl-2-methylbenzimidazole to the corresponding aldehyde using selenium dioxide was conducted according to a literature procedure (Werner et al. Tetrahedron, 1995, 51, 4779). 1-Ethyl-1H-benzimidazole-2-carboxaldehyde was isolated as a yellow oil in overall 52% yield.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH:28]=[O:29])=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].[BH4-].[Na+]>C(Cl)Cl.CO>[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][O:19][CH2:20][C:21]3[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][OH:29])=[CH:25][CH:26]=3)[CH2:13][CH2:14]2)=[N:7][CH:8]=1)[CH3:2]
Reactant: CCc1cnc(N2CCC([C@H]3C[C@H]3COCc3ccc(CC=O)cc3)CC2)nc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CCc1cnc(N2CCC([C@H]3C[C@H]3COCc3ccc(CCO)cc3)CC2)nc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The product of step B (70 mg, 0.18 mmol) was dissolved in DCM/MeOH (1/1, 4 mL) at 0° C., and sodium borohydride (30 mg, 0.8 mmol) added. The solution was stirred at 0° C. for 1 h. The solution was partitioned between water and DCM. The aqueous layer was extracted with DCM. The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified via silica gel column chromatography (2/1 hexanes/EtOAc) followed by reverse phase HPLC (C18, 10-100% water/acetonitrile with 0.1% formic acid gradient) which yielded the title compound. MS (ESI) m/z 396 [M+H]+. GPR119 Human EC50: 2.5 nM
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.Br[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH2:20][CH2:19][CH2:18][C:17]=2[CH:21]=[O:22])=[CH:12][CH:11]=1.C[Sn](C)C.C[Sn](C)C>O1CCOCC1.C(OCC)C.[F-].[Cs+].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>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH2:20][CH2:19][CH2:18][C:17]=3[CH:21]=[O:22])=[CH:12][CH:11]=2)=[N:3][CH:4]=1
Reactant: Fc1ccc(Br)nc1
Reactant: O=CC1=C(c2ccc(Br)cc2)CCC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Sn](C)C
Agent: [Cs+]
Solvent: CCOCC
Solvent: C1COCCO1
Product: O=CC1=C(c2ccc(-c3ccc(F)cn3)cc2)CCC1
Temperature: 110 °C
Reaction time: 72 h

Procedure:
Pd(PPh3)4 (230 mg, 0.20 mmol) was added to a solution of 2-bromo-5-fluoropyridine (350 mg, 2.0 mmol), 2-(4-bromophenyl)cyclopent-1-ene-1-carbaldehyde (500 mg, 2.0 mmol) and hexamethylditin (652 mg, 2.0 mmol) in degassed 1,4-dioxane (10 mL) at ambient temperature. After stirring at 110° C. for a further 3 days, the reaction mixture was diluted with diethyl ether and CsF/celite (1:1) was added. After stirring vigorously for 1 hr, reaction mixture was filtered and concentrated. Chromatography over silica eluting with 0-20% ethyl acetate/hexane afforded 2-[4-(5-fluoropyridin-2-yl)phenyl]cyclopent-1-ene-1-carbaldehyde as an orange gum.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH3:10]>CO>[Cl:1][C:2]1[N:7]=[C:6]([NH2:10])[C:5]([Cl:9])=[CH:4][N:3]=1
Reactant: N
Reactant: Clc1ncc(Cl)c(Cl)n1
Solvent: CO
Product: Nc1nc(Cl)ncc1Cl

Procedure:
A solution of 2,4,5-trichloropyrimidine (2.2 ml) in 2M ammonia in methanol (50 ml) was stirred at room temperature overnight. The reaction was then concentrated in vacuo and the resultant solid was washed with water. The residue was triturated with methanol and the solid was isolated by vacuum filtration to furnish the title compound as a white solid (487 mg). 1H NMR (400 MHz, DMSO-d6): 8.18 (1H, s).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=2[F:32])[C:27]#[N:28])[C:16](=[O:23])[C:17]#[C:18][Si](C)(C)C)[CH:12]=[CH:11][CH:10]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=2[F:32])[C:27]#[N:28])[C:16](=[O:23])[C:17]#[CH:18])[CH:12]=[CH:11][CH:10]=1
Reactant: C[Si](C)(C)C#CC(=O)C(c1cccc(-c2ccc(F)cc2F)n1)c1cc(C#N)ccc1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: C#CC(=O)C(c1cccc(-c2ccc(F)cc2F)n1)c1cc(C#N)ccc1F
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 71.7 %

Procedure:
To a solution of 3-[1-[6-(2,4-difluorophenyl)pyridin-2-yl]-2-oxo-4-(trimethylsilyl)but-3-yn-1-yl]-4-fluorobenzonitrile (from Step D above, 40 g, 89.0 mmol) in THF (750 mL) was added TBAF (133 mL, 133.6 mmol) at 0° C. After stirring at 0° C. for 15 min, the reaction was poured into aqueous NH4Cl, and extracted with EtOAc (2×). The organic layers were combined, washed with H2O, brine, dried over MgSO4. The mixture was concentrated and purified by silica gel chromatography (hexanes/methylene chloride) to give title compound (24 g). 1H NMR (CDCl3) δ: 7.80 (q, 1H), 7.72 (m, 3H), 7.51 (d, 1H), 7.31 (t, 1H), 7.04 (m, 1H), 6.97 (m, 1H), 6.60 (d, 1H), 3.14 (s, 10H).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[CH:15]=[CH:14][NH:13][C:12](=[O:17])[C:11]=2[CH:10]=[C:9]1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:20]Cl.F[B-](F)(F)F.C[O+](C)C>>[CH2:1]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[C:12]([O:17][CH3:20])[C:11]=2[CH:10]=[C:9]1[CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: ClCCl
Reactant: Cc1cc2c(=O)[nH]ccc2n1Cc1ccccc1
Agent: C[O+](C)C
Agent: F[B-](F)(F)F
Product: COc1nccc2c1cc(C)n2Cc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 31.2 %

Procedure:
To a mixture of 1-benzyl-2-methyl-1,5-dihydro-pyrrolo[3,2-c]pyridin-4-one (1) (3.48 g, 16.62 mmole) in dichloromethane (160 mL) trimethyloxonium tetrafluoroborate (4.52 g, 29.24 mmole) was added. The mixture was stirred at room temperature for 18 h. Additional trimethyloxonium tetrafluoroborate (2.25 g, 14.55 mmole) was added and stirred for 18 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography (20:1 CH2Cl2:MeOH) to afford intermediate (2) Yield: 1.31 g, 35%.
Reaction SMILES: O1CCCC1.[F:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:17](=O)[CH3:18])=[CH:9][CH:8]=1.[C:20]([S@:24]([NH2:26])=[O:25])([CH3:23])([CH3:22])[CH3:21].[BH4-].[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].O.CO>[F:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C@H:17]([NH:26][S:24]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:25])[CH3:18])=[CH:9][CH:8]=1
Reactant: CC(=O)c1ccc(F)c2ccccc12
Reactant: CC(C)(C)[S@](N)=O
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: [BH4-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: C[C@@H](NS(=O)C(C)(C)C)c1ccc(F)c2ccccc12
Temperature: -78 °C
Yield: 35.9 %

Procedure:
Titanium tetraisopropoxide (3.0 mL, 10 mmol) was added to a tetrahydrofuran (20 mL) solution of 4′-fluoro-1′-acetonaphthone 0.94 mL (6.0 mmol) and (R)-(+)-tert-butyl sulfinamide (610 mg, 5.0 mmol), and the mixture was heated under reflux for one full day. The reaction mixture was cooled to −78° C., followed by addition of sodium borohydride (0.76 g, 20 mmol), and then the temperature of the mixture was gradually raised to room temperature. Methanol (5 mL) and then water (20 mL) were added to the mixture under ice-cooling conditions, and the solid matter generated was filtered. The oil obtained was extracted with methylene chloride (20 mL), the organic phase was dried over sodium sulfate, and then the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate/hexane:67/33) to give the title compound (527 mg, 45%).
Reaction SMILES: [CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[SH:13].Cl[Sn:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[S:13][Sn:15]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: Cl[Sn](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cn1c(S)nc2ccccc2c1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cn1c(S[Sn](c2ccccc2)(c2ccccc2)c2ccccc2)nc2ccccc2c1=O
Yield: 61.6 %

Procedure:
A mixture of 11.6 g (0.06 mole) 3-methyl-2-mercapto-4(3H)-quinazolinone, 23.2 g (0.06 mole) chlorotriphenyl tin and 6.1 g (0.06 mole) triethylamine in methylene chloride (about 200 ml) were stirred together, then refluxed for four hours and stirred overnight. The reaction mixture was washed with water, dried and stripped. After trituration with ether, 20.0 g of the above-identified product as a white solid, melting point 155°-157° C. was obtained.