Hydrochloric Acid → HCID 178432001, compound

HRID 589712Notes

Reaction equation

C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[C:45]1[CH:46]=[CH:47][C:48]2[S:52][C:51]([S:53]([NH:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([C:63]4[NH:67][N:66]=[N:65][N:64]=4)[CH:58]=3)(=[O:55])=[O:54])=[C:50]([CH3:68])[C:49]=2[CH:69]=1.Cl.[OH-].[Na+]>C1COCC1>[CH3:68][C:50]1[C:49]2[CH:69]=[C:45]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[CH:46]=[CH:47][C:48]=2[S:52][C:51]=1[S:53]([NH:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([C:63]2[NH:64][N:65]=[N:66][N:67]=2)[CH:58]=1)(=[O:55])=[O:54]

Participants

Conditions

Temperature: 130 °C

Procedure

A micro-tube was charged with tris(benzylideneacetone)dipalladium (Pd2(dba)3) (0.5 mg, 0.0005 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.5 mg, 0.0012 mmol) and pyrrolidine (9 mg, 0.12 mmol). The tube was sealed and flushed with nitrogen. LiHMDS (1M in THF, 120 μL, 0.12 mmol) and a solution of 5-bromo-3-methyl-N-[3-(1H-tetrazol-5-yl)phenyl]-1-benzothiophene-2-sulfonamide (Example 34) (45 mg, 0.1 mmol) in dry THF were added to the reaction mixture via syringes. The reaction mixture was heated in a microwave reactor at 130° C. for 1000 s. Aqueous HCl (1 M) was added and the mixture was stirred at room temperature for 5 min. The solution was then neutralized by addition of aqueous NaOH. The crude product was purified by preparative HPLC (ACE C8, 5 μm 21×50 mm, flow 25 ml/min, 50 mM NH4OAc in water/CH3CN) to give 1.9 mg (4%) of the title compound. MS (ESI+) calcd for C20H20N6O2S2 440.108915, found 440.108815.

Workup

customThe tube was sealed
customflushed with nitrogen
customThe crude product was purified by preparative HPLC (ACE C8, 5 μm 21×50 mm, flow 25 ml/min, 50 mM NH4OAc in water/CH3CN)

Sources & evidence

ORD record: ord-3ef2461c36c94e8db0dc1571378225c7
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233946B2

Reaction notes

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