Sodium Carbonate → HCID 86680138, compound

HRID 1915940Notes

Reaction equation

HRID 1915940 reaction equation
Br[C:2]1[S:3][C:4]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[C:5]([C:7](=[O:31])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:30])[C:13]=2[N:14]2[CH2:20][CH2:19][C@@H:18]([F:21])[C@H:17]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:16][CH2:15]2)[N:6]=1.[CH3:40][C:41]1[CH:46]=[CH:45][N:44]=[CH:43][C:42]=1B(O)O.CC([O-])=O.[K+].C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:26]([O:25][C:23]([NH:22][C@H:17]1[C@H:18]([F:21])[CH2:19][CH2:20][N:14]([C:13]2[N:12]([CH3:30])[N:11]=[CH:10][C:9]=2[NH:8][C:7]([C:5]2[N:6]=[C:2]([C:42]3[CH:43]=[N:44][CH:45]=[CH:46][C:41]=3[CH3:40])[S:3][C:4]=2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:31])[CH2:15][CH2:16]1)=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 86680139HCID 86680139, compound

Product 1

HCID 86680138HCID 86680138, compoundYield 58.9%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

In a microwave reaction vial, tert-butyl N-[2-bromo-4-[[5-[(4R,5R)-4-(tert-butoxycarbonylamino)-5-fluoro-azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (161 mg, 0.25 mmol), (4-methyl-3-pyridyl)boronic acid (105 mg, 0.76) and PD(DPPF)CL2 (19 mg, 0.025 mmol) were dissolved in acetonitrile (3 mL). 1.0M KOAc (0.38 mL, 0.38 mmol) and 1.0M Na2CO3 (0.38 mL, 0.38 mmol) were added and the reaction was irradiated with microwave at 125° C. for 30 min. The mixture was cooled, filtered through Celite, concentrated and purified via flash chromatography, EA/heptane 0% to 100% to afford tert-butyl N-[4-[[5-[(4R,5R)-4-(tert-butoxycarbonylamino)-5-fluoro-azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]-2-(4-methyl-3-pyridyl)thiazol-5-yl]carbamate (95 mg, 58%). This compound was stirred with 4N HCl in dioxane (3 mL, 12 mmol) and methanol (2 mL) at room temperature for 3 h. Solvent was removed under reduced pressure. The residue was basified with saturated NaHCO3 and extracted with EA 3×. The combined organic layers were dried over MgSO4 and the solvent removed under reduced pressure and the residue purified by preparative HPLC to afford 428 (38 mg, 58%). 1H NMR (400 MHz, DMSO) δ 8.83 (s, 1H), 8.79 (s, 1H), 8.43 (d, J=5.0 Hz, 1H), 7.49 (s, 2H), 7.47 (s, 1H), 7.37 (d, J=4.9 Hz, 1H), 4.42 (dt, J=8.4, 5.0 Hz, 1H), 3.64 (s, 3H), 3.26-3.02 (m, 5H), 2.63 (s, 3H), 2.18-2.02 (m, 1H), 2.02-1.88 (m, 1H), 1.87-1.75 (m, 1H), 1.66-1.53 (m, 1H). LCMS (ES+) m/z 445 (M+1)

Workup

  1. customIn a microwave reaction vial
  2. customthe reaction was irradiated with microwave at 125° C. for 30 min
  3. temperatureThe mixture was cooled
  4. filtrationfiltered through Celite
  5. concentrationconcentrated
  6. custompurified via flash chromatography, EA/heptane 0% to 100%

Sources & evidence

ORD record
ord-1001350f71324211821a294d4b03d790
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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