Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH3:25])=[C:6]([C:8]2(Cl)[NH:13][C:12]([NH2:14])=[N:11][CH:10]=[CH:9]2)[CH:7]=1.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH3:25])=[C:6]([C:8]2[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([NH:33][C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)[CH:9]=2)[CH:7]=1
Reactant: COc1ccccc1COc1ccc(Br)cc1C1(Cl)C=CN=C(N)N1
Reactant: Nc1ccc(Cl)cc1
Product: COc1ccccc1COc1ccc(Br)cc1-c1cc(Nc2ccc(Cl)cc2)nc(N)n1
Yield: 57 %

Procedure:
Following the method described in Example 178, 6-[5-bromo-2-(2-methoxy-benzyloxy)-phenyl]-6-chloro-pyrimidin-2-ylamine and 4-chloro-phenylamine provided the title compound (57% yield). 1H NMR (CD3OD) δ 3.82 (s, 3H, CH3), 5.25 (s, 2H, CH2), 6.35 (s, 1H, Ar), 6.89-6.98 (m, 2H, Ar), 7.21-7.48 (m, 3H, Ar), 7.38-7.42 (m, 2H, Ar), 7.69-7.82 (m, 4H, Ar).
Reaction SMILES: [CH3:1][N:2]([CH3:47])[CH2:3][CH2:4][NH:5][C:6]([C@:8]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:9]1[C@@H:10]1[C@@:23]([CH3:26])([CH2:24][CH2:25]2)[C@@:22]2([CH3:27])[C@@H:13]([C@:14]3([CH3:40])[C@@H:19]([CH2:20][CH2:21]2)[C:18]([CH3:29])([CH3:28])[C:17]([C:30]2[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][CH:31]=2)=[CH:16][CH2:15]3)[CH2:12][CH2:11]1)=[O:7]>C(O)(=O)C.CO.[Pd]>[CH3:47][N:2]([CH3:1])[CH2:3][CH2:4][NH:5][C:6]([C@:8]12[CH2:43][CH2:42][C@@H:41]([CH:44]([CH3:45])[CH3:46])[C@@H:9]1[C@@H:10]1[C@@:23]([CH3:26])([CH2:24][CH2:25]2)[C@@:22]2([CH3:27])[C@@H:13]([C@:14]3([CH3:40])[C@@H:19]([CH2:20][CH2:21]2)[C:18]([CH3:28])([CH3:29])[C:17]([C:30]2[CH:31]=[CH:32][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:38][CH:39]=2)=[CH:16][CH2:15]3)[CH2:12][CH2:11]1)=[O:7]
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)NCCN(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: COC(=O)c1ccc(C2=CC[C@]3(C)[C@H]4CC[C@@H]5[C@H]6[C@H](C(C)C)CC[C@]6(C(=O)NCCN(C)C)CC[C@@]5(C)[C@]4(C)CC[C@H]3C2(C)C)cc1
Yield: 22.1 %

Procedure:
A mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)ethylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (27 mg, 0.042 mmol) and Pd/C (14.30 mg, 0.013 mmol) in acetic acid (4 mL) and MeOH (4 mL) was reacted in Parr shaker for 18 hours under 40 psi. The reaction mixture was filtered through celite to remove Pd/C. The filtrates were concentrated under reduced pressure. The residue was dissolved in methanol and then purified by prep HPLC to provide the title compound as a white solid (6 mg, 22%). LCMS: m/e 645.62 (M+H)+, 2.87 min (method 1). 1H NMR (500 MHz, Acetic Acid-d4) δ ppm 7.98 (d, J=8.24 Hz, 2H), 7.27 (d, J=8.24 Hz, 2H), 5.37 (d, J=4.88 Hz, 1H), 3.94 (s, 3H), 3.74 (t, J=5.95 Hz, 2H), 3.43-3.32 (m, 2H), 2.95 (s, 6H), 2.59-2.48 (m, 1H), 2.42-2.31 (m, 1H), 2.28-1.10 (m, 22H), 1.07 (d, J=3.97 Hz, 6H), 1.05 (s, 3H), 1.00 (s, 3H), 0.99 (s, 3H), 0.91 (d, J=6.71 Hz, 3H), 0.82 (d, J=6.71 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:30]=[C:31]([NH:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[CH:32]=[CH:33][C:34]=2[F:35])[CH2:25][CH2:24]1>C(Cl)(Cl)Cl>[CH3:18][C:15]1[CH:16]=[CH:17][C:12]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[C:9]([NH:19][CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([C:29]3[CH:30]=[C:31]([NH:36][C:37](=[O:41])[CH:38]([CH3:39])[CH3:40])[CH:32]=[CH:33][C:34]=3[F:35])[CH2:25][CH2:24]2)=[O:11])=[CH:13][CH:14]=1
Reactant: CC(C)C(=O)Nc1ccc(F)c(C2CCN(CCCN)CC2)c1
Reactant: Cc1ccc(C(C(=O)O)c2ccc(C)cc2)cc1
Solvent: ClC(Cl)Cl
Product: Cc1ccc(C(C(=O)NCCCN2CCC(c3cc(NC(=O)C(C)C)ccc3F)CC2)c2ccc(C)cc2)cc1

Procedure:
Example 132 was prepared from bis(4-methylphenyl)acetic acid and N-{3-[1-(3-aminopropyl)-4-piperidinyl]-4-fluorophenyl}-2-methylpropanamide according to the procedures described in Scheme 9: 1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 7.36–7.31 (m, 1H), 7.28–7.21 (m, 1H), 7.12–7.07 (m, 3H), 7.03–6.99 (m, 5H), 6.86–6.80 (m, 1H), 6.79–6.75 (m, 1H), 4.74 (s, 1H), 3.33–3.25 (m, 2H), 2.85–2.77 (m, 2H), 2.72–2.62 (m, 1H), 2.40 (septet, 1H, J=6.7 Hz), 2.28 (t, 2H, J=6.6 Hz), 2.21 (m, 6H), 1.94–1.84 (m, 2H), 1.65–1.52 (m, 6H), 1.71 (d, 6H, J=6.6 Hz); ESMS m/e: 544.3 (M+H)+; Anal. Calc. for C34H42FN3O2.HCl.0.10 CHCl3: C, 70.17; H, 7.35; N, 7.10. Found: C, 70.35; H, 6.99; N, 7.10.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:8]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[CH3:20])[CH:9]=[CH:10][CH:11]=1.[C:21](=O)([O-])[O-:22].[Na+].[Na+]>CN(C=O)C>[Br:6][C:7]1[N:8]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[CH3:20])[C:9]([CH:21]=[O:22])=[CH:10][CH:11]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1cc(C#N)ccc1-n1cccc1Br
Agent: [Na+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: Cc1cc(C#N)ccc1-n1c(Br)ccc1C=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 58 %

Procedure:
DMF (0.1 mL) was added to phosphorus oxychloride (0.5 mL, 5.2 mmol) at 0° C., and the mixture was stirred at room temperature for 1.5 h. At 0° C., a solution of compound 50B (100 mg. 0.36 mmol) in DMF (2 mL) was added, and the resultant mixture was stirred at room temperature for 30 min. The reaction mixture was poured into ice-water, adjusted to pH=8 with saturated aqueous sodium carbonate solution, and extracted with ethyl acetate (10 mL×3). The combined organic layers were washed with brine (20 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC to afford 50C (60 mg, yield 58%).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].CC(C)(C)[CH2:10][NH:11][CH2:12][C:13]1[O:17][CH:16]=[C:15]([C:18]2[CH:19]=[C:20]3[C:24](=[C:25]([C:27]([NH2:29])=[O:28])[CH:26]=2)[NH:23][CH:22]=[C:21]3[CH:30]2[CH2:35][CH2:34][N:33]([S:36]([CH2:39][CH3:40])(=[O:38])=[O:37])[CH2:32][CH2:31]2)[CH:14]=1.[CH3:43][C:44](C)(C)[CH2:45]N>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:39]([S:36]([N:33]1[CH2:32][CH2:31][CH:30]([C:21]2[C:20]3[C:24](=[C:25]([C:27]([NH2:29])=[O:28])[CH:26]=[C:18]([C:15]4[CH:14]=[C:13]([CH2:12][N:11]5[CH2:10][CH2:45][CH2:44][CH2:43]5)[O:17][CH:16]=4)[CH:19]=3)[NH:23][CH:22]=2)[CH2:35][CH2:34]1)(=[O:38])=[O:37])[CH3:40]
Reactant: CC(C)(C)CN
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4coc(CNCC(C)(C)C)c4)cc23)CC1
Solvent: O=C(O)C(F)(F)F
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4coc(CN5CCCC5)c4)cc23)CC1
Yield: 7.2 %

Procedure:
The title compound was prepared according to the general procedure of 5-(5-{[(2,2-dimethylpropyl)amino]methyl}-3-furanyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide trifluoroacetate, substituting pyrrolidine (99.6 mg, 1.4 mmol) for 2,2-dimethyl-1-propanamine to afford 6 mg of the title compound (7.2%).
Reaction SMILES: [CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Br[C:42]1[N:50]=[CH:49][CH:48]=[C:47]2[C:43]=1[CH:44]=[CH:45][NH:46]2>>[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([C:42]1[C:43]3[CH:44]=[CH:45][NH:46][C:47]=3[CH:48]=[CH:49][N:50]=1)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nc(N2CCOCC2)c2nc(CN3CCC(C(C)(C)O)CC3)n(C)c2n1
Reactant: Brc1nccc2[nH]ccc12
Product: Cn1c(CN2CCC(C(C)(C)O)CC2)nc2c(N3CCOCC3)nc(-c3nccc4[nH]ccc34)nc21

Procedure:
2-(1-((9-Methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (150 mg) was reacted with 4-bromo-5-azaindole via General Procedure G to afford 119 (20 mg) following reverse phase purification. MS (Q1) 491.2 (M)+. 1H NMR (400 MHz, MeOD) δ 8.31 (d, 1H), 7.51 (d, 1H), 7.45 (d, 1H), 7.34 (d, 1H), 4.39 (s, 4H), 4.03-3.69 (m, 10H), 3.31 (d, 5H), 3.01 (d, 2H), 2.10 (t, 2H), 2.03 (s, 2H), 1.75 (d, 2H), 1.53-1.22 (m, 4H), 1.13 (s, 6H)
Reaction SMILES: [CH3:1][N:2]([CH3:14])[S:3]([C:6]1[S:10][C:9]([N:11]=[C:12]=[O:13])=[N:8][N:7]=1)(=[O:5])=[O:4].[O:15]1[CH2:19][CH2:18][O:17][CH:16]1[CH2:20][NH:21][CH3:22]>C(OCC)(=O)C>[CH3:1][N:2]([CH3:14])[S:3]([C:6]1[S:10][C:9]([NH:11][C:12]([N:21]([CH2:20][CH:16]2[O:17][CH2:18][CH2:19][O:15]2)[CH3:22])=[O:13])=[N:8][N:7]=1)(=[O:5])=[O:4]
Reactant: CNCC1OCCO1
Reactant: CN(C)S(=O)(=O)c1nnc(N=C=O)s1
Solvent: CCOC(C)=O
Product: CN(CC1OCCO1)C(=O)Nc1nnc(S(=O)(=O)N(C)C)s1

Procedure:
5-(N,N-Dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl isocyanate dimer (6 grams), N-(1,3-dioxolan-2-ylmethyl)-N-methylamine (6 grams) and ethyl acetate (20 ml) were charged into a glass reaction vessel fitted with a mechanical stirrer. The reaction mixture was heated on a steam bath for a period of about 2 hours. Solvent was then stripped off using a rotary evaporator to yield the desired product N-[5-(N,N-dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl]-N'-(1,3-dioxolan-2-ylmethyl)-N'-methylurea as the residue. Melting point 100°-110° C.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Na+].Br[CH2:18][CH2:19][CH2:20][CH2:21][Cl:22].O>CS(C)=O>[Cl:22][CH2:21][CH2:20][CH2:19][CH2:18][N:6]1[CH:7]=[C:2]([CH3:1])[C:3]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:4][C:5]1=[O:8]
Reactant: ClCCCCBr
Reactant: Cc1c[nH]c(=O)nc1-c1cccnc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1cn(CCCCCl)c(=O)nc1-c1cccnc1
Temperature: 60 °C
Yield: 67.9 %

Procedure:
To a solution of 5-methyl-4-pyridin-3-yl-1H-pyrimidin-2-one (100 mg, 0.53 mmol) in DMSO (2 ml), 60% NaH (23 mg, 0.59 mmol) was added portionwise. After heating the mixture at 60° C. for 1 hour, 1-bromo-4-chloro-butane (100 mg, 0.59 mmol) dissolved in DMSO (0.8 ml) was added at 60° C. and the heating was maintained for further 2 hours. After cooling to room temperature, water was added and the mixture extracted with diethyl ether to remove the dialkylated product and finally with ethyl acetate. Ethyl acetate was washed with brine, dried (Na2SO4) and evaporated to afford 100 mg of the title compound as yellow oil (68% yield).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C(N(CC)CC)C.Cl.[N:17]1([CH2:23][CH2:24][C:25]2[N:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]3=[C:27]([C:34](Cl)=[O:35])[N:26]=2)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:34]([C:27]2[N:26]=[C:25]([CH2:24][CH2:23][N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[N:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=23)=[O:35])[CH:6]=[CH:7][CH:8]=1
Reactant: O=C(Cl)c1nc(CCN2CCOCC2)n2ccccc12
Reactant: Nc1cccc(F)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1cccc(F)c1)c1nc(CCN2CCOCC2)n2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 18.1 %

Procedure:
To a solution of 3-fluoroaniline (0.052 mL, 0.54 mmol) and triethylamine (0.16 mL, 1.14 mmol) in CH2Cl2 (10 mL) was added 3-(2-morpholin-4-yl-ethyl)-imidazo[1,5-a]pyridine-1-carbonyl chloride hydrochloride (150 mg, 0.45 mmol). The mixture was stirred at ambient temperature for 1 h then washed with sat. aq. NaHCO3 (20 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica to yield the title compound (30 mg, 18%). 1H NMR (DMSO-d6) δ 10.02 (1H), 8.45 (1H), 8.15 (1H), 7.88 (1H), 7.70 (1H), 7.43 (1H), 7.20 (1H), 6.95 (1H), 6.85 (1H), 3.58 (4H), 3.25 (2H), 2.80 (2H), 2.44 (4H); m/z (M+H)=369.22.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH:6]1[C:10]2[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:9]=2[O:8][CH2:7]1)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>C1COCC1>[NH2:1][CH2:4][CH2:5][CH:6]1[C:10]2[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:9]=2[O:8][CH2:7]1
Reactant: N#Cc1ccc2c(c1)C(CCN=[N+]=[N-])CO2
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: N#Cc1ccc2c(c1)C(CCN)CO2
Reaction time: 7 h

Procedure:
To a solution of 3-(2-azido-ethyl)-5-cyano-2,3-dihydro-benzofuran (434 mg, 2 mmol) (reference example 7) in THF (10 mL) was added Ph3P (576 mg, 2.2 mmol). The resulting solution was stirred for 7 hr then H2O added (72 ml, 4 mmol). This solution was stirred for 18 hr then concentrated. The residue was azeotroped with toluene then used without further purification. 1H NMR (CDCl3) d 1.81 (m, 1H), 1.93 (m, 1H) 2.5 (bs, 2H), 2.81 (m, 2H), 3.60 (m, 1H), 4.32 (dd, J=8, 6 Hz, 1H), 4.73 (t, J=8 Hz, 1H) 6.83 (d, J=8 Hz, 1H), 7.46 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](O)=[O:24])=[CH:18][CH:17]=1.C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[CH:34]=1>C(Cl)Cl>[CH:38]([C:35]1[CH:34]=[C:33]([NH:32][C:23](=[O:24])[CH2:22][C:19]2[CH:18]=[CH:17][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)=[CH:21][CH:20]=2)[O:37][N:36]=1)([CH3:40])[CH3:39]
Reactant: COc1cc2ncnc(Oc3ccc(CC(=O)O)cc3)c2cc1OC
Reactant: CC(C)c1cc(N)on1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: COc1cc2ncnc(Oc3ccc(CC(=O)Nc4cc(C(C)C)no4)cc3)c2cc1OC
Temperature: 60 °C
Yield: 46.3 %

Procedure:
A mixture of 2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetic acid (0.3 g) and oxalyl chloride (3.73 ml) was heated at 60° C. for 30 minutes. The excess of oxalyl chloride was evaporated. Pyridine (0.43 ml) was added to a stirred mixture of the 2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetyl chloride so obtained, 5-amino-3-isopropylisoxazole (0.148 g) and methylene chloride (30 ml). The resultant mixture was stirred at ambient temperature for 30 minutes. The mixture was evaporated and the residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and ethyl acetate as eluent. There was thus obtained the title compound (0.183 g); 1H NMR: (DMSOd6) 1.89 (d, 6H), 2.92 (m, 1H), 3.75 (s, 2H), 3.97 (s, 3H), 4.0 (s, 3H), 6.18 (s, 1H), 7.26 (d, 2H), 7.39 (s, 1H), 7.41 (d, 2H), 7.55 (s, 1H), 8.53 (s, 1H), 11.83 (br s, 1H); Mass Spectrum: M+H+ 449.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:18]([O:22][C:23](=[O:26])[CH2:24]Br)([CH3:21])([CH3:20])[CH3:19]>CC#N.C(Cl)Cl>[CH2:1]([N:8]([CH2:9][CH2:10][OH:11])[CH2:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCCNCc1ccccc1
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC#N
Product: CC(C)(C)OC(=O)CN(CCO)Cc1ccccc1
Temperature: 25 °C
Reaction time: 66 h
Yield: 90.1 %

Procedure:
To a solution of Compound 2 (1.86 g, 12.3 mmol) and potassium carbonate (1.70 g, 12.3 mmol) in CH3CN anhydrous (50 mL) at 0° C. was dropwise added t-Butyl-bromoacetate (2.41 g, 12.4 mmol) over 45 minute. The reaction mixture was gradually warmed to room temperature and stirred for 66 h. The resulting reaction mixture was filtered, and the filtrate was concentrated to give a white oily compound. The residue was then dissolved in CH2Cl2 (50 mL), and the resulting solution was filtered, and the filtrate was concentrated to afford white Compound 4 (2.94 g, 90%), 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.86 (t, 2H), 3.23 (s, 2H), 3.54 to 3.62 (m, 2H), 3.82 (s, 2H), 7.23 to 7.34 (m, 5H); 13C NMR (CDCl3) δ 28.00, 55.27, 26.52, 58.47, 58.84, 81.29, 127.28, 128.36, 128.81, 138.27, 171.02. HRMS (Positive ion FAB) Calcd for C15H24NO3 [M+H]+ m/z 266.3605. Found: [M+H]+ m/z 266.1756.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([C:11]#[N:12])[N:8]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:6]=2[N:7]=1.[C:18]([SiH2:22][O:23][C:24]([CH3:33])([CH3:32])[C:25]1[CH:26]=[CH:27][C:28]([NH2:31])=[N:29][CH:30]=1)([CH3:21])([CH3:20])[CH3:19]>>[C:18]([SiH2:22][O:23][C:24]([CH3:33])([CH3:32])[C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:2]2[N:3]=[CH:4][C:5]3[CH:10]=[C:9]([C:11]#[N:12])[N:8]([CH:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)[C:6]=3[N:7]=2)=[N:29][CH:30]=1)([CH3:21])([CH3:19])[CH3:20]
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1ccc(N)nc1
Reactant: N#Cc1cc2cnc(Cl)nc2n1C1CCCC1
Product: CC(C)(C)[SiH2]OC(C)(C)c1ccc(Nc2ncc3cc(C#N)n(C4CCCC4)c3n2)nc1
Yield: 66 %

Procedure:
Following Buchwald Procedure A, 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitrile (95 mg, 0.385 mmol) and 5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (101 mg, 0.424 mmol) (Example C) gave 114 mg of 2-[5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamino]-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitrile [following SiO2 chromatography eluting with 1-2% MeOH/dichloromethane and subsequent trituration with diethyl ether].
Reaction SMILES: C(N(C(C)C)CC)(C)C.[F:10][C:11]([F:24])([F:23])[S:12]([O:15]S(C(F)(F)F)(=O)=O)(=[O:14])=[O:13].[CH2:25]([C:27]([C:45]1[CH:50]=[C:49]([CH3:51])[C:48](O)=[C:47]([CH3:53])[CH:46]=1)([C:30]1[CH:35]=[CH:34][C:33](/[CH:36]=[CH:37]/[C:38]([CH2:42][CH3:43])([OH:41])[CH2:39][CH3:40])=[C:32]([CH3:44])[CH:31]=1)[CH2:28][CH3:29])[CH3:26].C(=O)(O)[O-].[Na+]>ClCCl>[CH2:25]([C:27]([C:45]1[CH:46]=[C:47]([CH3:53])[C:48]([O:15][S:12]([C:11]([F:24])([F:23])[F:10])(=[O:14])=[O:13])=[C:49]([CH3:51])[CH:50]=1)([C:30]1[CH:35]=[CH:34][C:33](/[CH:36]=[CH:37]/[C:38]([CH2:39][CH3:40])([OH:41])[CH2:42][CH3:43])=[C:32]([CH3:44])[CH:31]=1)[CH2:28][CH3:29])[CH3:26]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CCC(O)(/C=C/c1ccc(C(CC)(CC)c2cc(C)c(O)c(C)c2)cc1C)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCC(O)(/C=C/c1ccc(C(CC)(CC)c2cc(C)c(OS(=O)(=O)C(F)(F)F)c(C)c2)cc1C)CC
Temperature: -40 °C
Reaction time: 0.17 h
Yield: 85.8 %

Procedure:
Diisopropylethylamine (2.2 mL, 12.92 mmol) and trifluoromethanesulfonic anhydride (1.3 mL, 7.75 mmol) were added to a solution of 4-{1-ethyl-1-[(E)-4-(3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-2,6-dimethyl-phenol (Example 38-(4); 2.55 g, 6.46 mmol) in dichloromethane (30 mL) at −40° C., and the mixture was stirred at −40° C. for 10 minutes. A saturated aqueous sodium bicarbonate solution was added to the reaction mixture, which was then heated to room temperature and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 50:50, 40 minutes) to give the target compound as a colorless oil (2.92 g, 86%).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:21]([O:28][C:29](=[O:33])[CH2:30][CH2:31][NH2:32])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C>CN(C)C=O>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7]([NH:32][CH2:31][CH2:30][C:29]([O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:33])=[O:9])=[CH:3]1
Reactant: Cn1ccc(C(=O)O)c1
Reactant: NCCC(=O)OCc1ccccc1
Agent: CCOP(=O)(C#N)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1ccc(C(=O)NCCC(=O)OCc2ccccc2)c1

Procedure:
Into a solution of 5.01 g (40 mmol) of 1-methyl-3-pyrrolecarboxylic acid and 16.87 g (48 mmol) of β-alanine benzyl ester p-toluenesulfonate in 200 ml of dimethylformamide (hereinafter called “DMF”), a solution of 7.83 g (48 mmol) of diethyl phosphorocyanidate in 50 ml of DMF was added dropwise under ice cooling and stirring. A solution of 9.71 g (96 mmol) of triethylamine in 50 ml of DMF was then added dropwise, and the reaction mixture was stirred at room temperature for 67 hours.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:20][C@@H:19]([C:21]2[CH:32]=[CH:31][C:24]3[O:25][C:26]([CH3:30])([CH3:29])[O:27][CH2:28][C:23]=3[CH:22]=2)[O:18][C:17]1=[O:33].[CH:37]1([N:43]=[C:44]=[O:45])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.C(O)(C)C>ClCCl>[CH:37]1([NH:43][C:44]([NH:1][C:2]2[CH:36]=[CH:35][CH:34]=[C:4]([CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:20][C@@H:19]([C:21]4[CH:32]=[CH:31][C:24]5[O:25][C:26]([CH3:30])([CH3:29])[O:27][CH2:28][C:23]=5[CH:22]=4)[O:18][C:17]3=[O:33])[CH:3]=2)=[O:45])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(N)c4)C(=O)O3)ccc2O1
Reactant: O=C=NC1CCCCC1
Solvent: ClCCl
Solvent: CC(C)O
Product: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(NC(=O)NC5CCCCC5)c4)C(=O)O3)ccc2O1
Temperature: 20 °C
Reaction time: 3 h
Yield: 81.1 %

Procedure:
A solution of (5R)-3-(6-{2-[(3-aminobenzyl)oxy]ethoxy}hexyl)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3oxazolidin-2-one (0.209 g) in dichloromethane (4 ml) was treated with cyclohexyl isocyanate (0.075 g) and the mixture stirred under nitrogen at 20° C. for 3 h. At this point further cyclohexyl isocyanate (0.150 g) was added, and the reaction mixture stirred for a further 65 h. Isopropanol (15 ml) was added to quench excess isocyanate, and the mixture stirred for 3 h. The solvents were removed in vacuo to give a residue which was purified by Biotage. Elution with 6:4 EtOAc/cyclohexane followed by solvent evaporation in vacuo gave the title compound (0.212 g). LCMS RT=3.77 min, ES+ve 624 (MH)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:14]([O:16][CH2:17]C)=[O:15])[NH:7]2.[Mg].ClCCl.[NH4+].[Cl-]>CO>[CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH:6]([C:14]([O:16][CH3:17])=[O:15])[NH:7]2
Reactant: CCOC(=O)c1cc2c(OC)c(OC)ccc2[nH]1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CO
Product: COC(=O)C1Cc2c(ccc(OC)c2OC)N1
Temperature: 25 °C

Procedure:
Ethyl 4,5-dimethoxyindole-2-carboxylate (0.500 g, 2 mmol) was dissolved in methanol (10 ml) and magnesium shavings (0.2431 g, 10 mmol) were then added, with stirring, at room temperature under a nitrogen atmosphere. After the reaction started, a water bath was used to maintain the reaction temperature between 5-15° C. At the end of the reaction, dichloromethane (200 ml) was added to the mixture, followed by NH4Cl solution (200 ml). The organic phase was separated out and the aqueous phase was extracted with dichloromethane (3×50 ml). The combined organic phases were dried over magnesium sulphate and the solvent was removed to give a brown oil.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([O:15][CH3:16])[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:17]#[N:18].[Br:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23].C(=O)(O)[O-].[Na+]>C(O)C>[N+:12]([C:9]1[CH:10]=[C:11]2[C:6](=[C:7]([O:15][CH3:16])[CH:8]=1)[N:5]=[CH:4][C:3]([C:17]#[N:18])=[C:2]2[NH:23][C:22]1[CH:24]=[CH:25][CH:26]=[C:20]([Br:19])[CH:21]=1)([O-:14])=[O:13]
Reactant: Nc1cccc(Br)c1
Reactant: COc1cc([N+](=O)[O-])cc2c(Cl)c(C#N)cnc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: COc1cc([N+](=O)[O-])cc2c(Nc3cccc(Br)c3)c(C#N)cnc12
Yield: 75.8 %

Procedure:
A mixture of 1.9 g (7.6 mmol) of 4-chloro-8-methoxy-6-nitro-quinoline-3-carbonitrile and 0.86 ml (8.3 mmol) of 3-bromo aniline in 95 ml ethanol was refluxed under nitrogen for 5 hours. The reaction mixture was poured into diluted sodium bicarbonate solution. Ethanol was removed under vacuum. The mixture was diluted with ethyl acetate and the organic layer was separated and dried over sodium chloride. The solution was concentrated and solid was collected and then washed with hexane. Upon drying, 2.3 g of yellow solid obtained: mass spectrum (electrospray, m/e) M+H 398.8 and 400.8.