Potassium Phosphate, Tribasic → HCID 131732732, compound

HRID 1470973Notes

Reaction equation

HRID 1470973 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]([C:13]3[CH:18]=[CH:17][C:16]([C@:19]4([C:35](=[O:37])[NH2:36])[CH2:23][CH2:22][CH2:21][N:20]4[C:24](=[O:34])[C@@H:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:26]([CH3:28])[CH3:27])=[CH:15][CH:14]=3)[CH2:11][CH2:10][CH:9]2[C:38]2[CH:43]=[CH:42][C:41]([C@:44]3([C:60](=[O:62])[NH2:61])[CH2:48][CH2:47][CH2:46][N:45]3[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:53])[CH3:52])=[CH:40][CH:39]=2)=[CH:4][CH:3]=1.[C:63]1(B(O)O)[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:2]1([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([C@:19]4([C:35](=[O:37])[NH2:36])[CH2:23][CH2:22][CH2:21][N:20]4[C:24](=[O:34])[C@@H:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:26]([CH3:28])[CH3:27])=[CH:15][CH:14]=3)[CH2:11][CH2:10][C@@H:9]2[C:38]2[CH:43]=[CH:42][C:41]([C@:44]3([C:60](=[O:62])[NH2:61])[CH2:48][CH2:47][CH2:46][N:45]3[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:53])[CH3:52])=[CH:40][CH:39]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 131732733HCID 131732733, compound

Product 1

HCID 131732732HCID 131732732, compoundYield 75.4%

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The product from Example 86C (24.9 mg, 0.027 mmole) dissolved in a THF (1 mL) and water (0.3 mL) solution was combined in a microwave tube with phenylboronic acid (6.90 mg, 0.054 mmole), tribasic potassium phosphate (13.37 mg, 0.063 mmole) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (1.42 mg, 2.17 μmole). The tube was sealed and nitrogen bubbled through at room temperature for five minutes. All gas lines were subsequently removed and the reaction vessel immersed in a 50° C. oil bath and heated for two and one half hours. The contents of the tube were partitioned between ethylacetate (5 mL) and brine (1 mL). The organic phase was washed with brine (2×1 mL) then dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with 5% EtOAc-hexane and progressing to (75% EtOAc-hexane)+3% methanol to provide as a 1:1 mixture of (trans) diastereomers the title compound (18.6 mg, 75% yield) as a cream colored solid. 1H NMR (400 MHz, DMSO-D6) δ ppm 0.76-0.99 (m, 12H) 1.67 (s, 2H) 1.77-2.19 (m, 11H) 3.52 (s, 6H) 3.58-3.65 (m, 2H) 3.74-3.86 (m, 2H) 3.96-4.08 (m, 2H) 4.44 (d, J=4.99 Hz, 2H) 5.25 (s, 2H) 6.35 (d, J=8.02 Hz, 2H) 7.17 (d, J=7.26 Hz, 5H) 7.24-7.34 (m, 6H) 7.45 (d, J=7.92 Hz, 2H) 7.52 (d, J=7.81 Hz, 4H) 10.00 (s, 2H). MS ESI(+) m/[email protected] (M+H)+, m/[email protected] (M+CH3CN+NH4)+.

Workup

  1. customThe tube was sealed
  2. customnitrogen bubbled through at room temperature for five minutes
  3. customAll gas lines were subsequently removed
  4. customimmersed in a 50° C.
  5. temperatureheated for two and one half hours
  6. customThe contents of the tube were partitioned between ethylacetate (5 mL) and brine (1 mL)
  7. washThe organic phase was washed with brine (2×1 mL)
  8. dry with materialthen dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by silica gel chromatography
  12. washeluting with 5% EtOAc-hexane and progressing to (75% EtOAc-hexane)+3% methanol
  13. customto provide as a 1:1 mixture of (trans)

Sources & evidence

ORD record
ord-9bc74619218241df9e1366f8888eef80
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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