Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.CC(C)([O-])C.[Na+].C1COCC1.Cl.Cl.[NH2:21][CH2:22][CH2:23][NH:24][C@:25]12[CH2:60][CH2:59][C@@H:58]([C:61]([CH3:63])=[CH2:62])[C@@H:26]1[C@@H:27]1[C@@:40]([CH3:43])([CH2:41][CH2:42]2)[C@@:39]2([CH3:44])[C@@H:30]([C@:31]3([CH3:57])[C@@H:36]([CH2:37][CH2:38]2)[C:35]([CH3:46])([CH3:45])[C:34]([C:47]2[CH:56]=[CH:55][C:50]([C:51]([O:53]C)=[O:52])=[CH:49][CH:48]=2)=[CH:33][CH2:32]3)[CH2:29][CH2:28]1.O.[OH-].[Li+].C(O)(C(F)(F)F)=O>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO.O>[CH3:43][C@:40]12[C@@:39]3([CH3:44])[C@@H:30]([C@:31]4([CH3:57])[C@@H:36]([CH2:37][CH2:38]3)[C:35]([CH3:45])([CH3:46])[C:34]([C:47]3[CH:56]=[CH:55][C:50]([C:51]([OH:53])=[O:52])=[CH:49][CH:48]=3)=[CH:33][CH2:32]4)[CH2:29][CH2:28][C@@H:27]1[C@H:26]1[C@H:58]([C:61]([CH3:63])=[CH2:62])[CH2:59][CH2:60][C@:25]1([NH:24][CH2:23][CH2:22][NH:21][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[CH2:42][CH2:41]2
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCN)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
Reactant: Brc1cccnc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: CO
Solvent: C1CCOC1
Solvent: COCCOC
Product: C=C(C)[C@@H]1CC[C@]2(NCCNc3cccnc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 110 °C
Reaction time: 0.17 h
Yield: 82.4 %

Procedure:
In a 1 dram vial under nitrogen were combined (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (CAS#158923-11-6) (2.101 mg, 3.79 mmol), palladium(II) acetate (0.851 mg, 3.79 mmol) and dry DME (0.5 ml). The contents of the vial were stirred for 10 min, and were then added all at once to a separate mixture of 3-bromopyridine (0.014 g, 0.091 mmol) and sodium tert-butoxide, 2.0M solution in THF (0.167 mL, 0.333 mmol) in dry DME (0.333 mL) contained in a separate 1 dram vial. The resulting mixture was allowed to stir very briefly (1 min) before solid methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-aminoethylamino)-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 bis HCl salt (0.050 g, 0.076 mmol) was added in one portion. The mixture was heated to 110° C. overnight. To the mixture was added lithium hydroxide monohydrate (6.4 mg, 0.152 mmol) with water (0.2 mL) and methanol (0.5 mL) and the resulting mixture was stirred for 4 days. Purification of the crude mixture by reverse phase preparative HPLC using Prep HPLC Method 7 gave the title compound (0.0407 g, 57.5% yield) as a beige powder bis TFA salt. LCMS: m/e 650.4 (M+H)+, 2.26 min (method 11). 1H NMR (500 MHz, 1:1 mixture of CDCl3 and MeOD, MeOD lock) δ ppm 8.26 (d, J=2.4 Hz, 1H), 8.02 (d, J=4.9 Hz, 1H), 7.94-7.87 (m, J=8.2 Hz, 2H), 7.77 (dd, J=8.9, 1.5 Hz, 1H), 7.67 (dd, J=8.9, 5.2 Hz, 1H), 7.22-7.14 (m, 2H), 5.28 (dd, J=6.3, 1.7 Hz, 1H), 4.82 (s, 1H), 4.74 (s, 1H), 3.89-3.78 (m, 1H), 3.70 (dt, J=14.6, 4.5 Hz, 1H), 3.30-3.23 (m, 2H), 2.85 (td, J=11.1, 5.5 Hz, 1H), 2.21-2.05 (m, 3H), 2.03-1.94 (m, 2H), 1.94-1.85 (m, 1H), 1.85-1.76 (m, 1H), 1.72 (s, 3H), 1.70-1.64 (m, 1H), 1.64-1.51 (m, 3H), 1.51-1.44 (m, 3H), 1.43-1.20 (m, 6H), 1.19-1.08 (m, 2H), 1.07-1.04 (m, 3H), 1.04-1.00 (m, 3H), 0.99 (s, 3H), 0.95-0.88 (m, 7H).