Sodium Carbonate → HCID 70652051, compound

HRID 1426062Notes

Reaction equation

HRID 1426062 reaction equation
[CH:1]1([CH2:4][C@:5]2([CH2:29][C:30]([OH:33])([CH3:32])[CH3:31])[O:10][C:9](=[O:11])[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][C:17](B4OC(C)(C)C(C)(C)O4)=[CH:16][CH:15]=3)[CH3:13])[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.Br[C:35]1[CH:36]=[CH:37][C:38]([C:41]2([C:44]([NH2:46])=[O:45])[CH2:43][CH2:42]2)=[N:39][CH:40]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([CH2:4][C@:5]2([CH2:29][C:30]([OH:33])([CH3:32])[CH3:31])[O:10][C:9](=[O:11])[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][C:17]([C:35]4[CH:36]=[CH:37][C:38]([C:41]5([C:44]([NH2:46])=[O:45])[CH2:43][CH2:42]5)=[N:39][CH:40]=4)=[CH:16][CH:15]=3)[CH3:13])[CH2:7][CH2:6]2)[CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 67996687HCID 67996687, compoundHCID 67997485HCID 67997485, compound

Product 1

HCID 70652051HCID 70652051, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (3.3 mg) was added to a solution of (S)-6-(cyclopropylmethyl)-6-(2-hydroxy-2-methylpropyl)-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-1,3-oxazinan-2-one (150 mg), 1-(5-bromopyridin-2-yl)cyclopropanecarboxamide (94 mg), and Na2CO3 (348 mg, 3.28 mmol) in ethanol (8 mL), toluene (12 mL), and H2O (4 mL) at room temperature. The reaction mixture was heated to 100° C. for 2 h. After cooling to room temperature, the formed mixture was concentrated to afford an oil which was diluted with H2O (30 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was concentrated to afford an oil which was purified by preparative TLC and preparative HPLC to give the title compound. Yield: 30 mg (19% of theory); LC (method 4): tR=0.95 min, Mass spectrum (ESI+): m/z=492 [M+H]+; 1H NMR (CDCl3, 400 MHz) δ 0.01 (d, 2H), 0.40-0.50 (m, 2H), 0.69 (m, 1H), 1.27 (m, 2H), 1.33 (s, 3H), 1.39 (s, 3H), 1.61 (d, 3H), 1.78 (m, 1H), 1.82 (m, 2H), 1.89-2.05 (m, 4H), 2.21 (m, 1H), 2.80 (m, 1H), 3.19 (m, 1H), 5.51 (1H), 5.85 (m, 1H), 7.29 (m, 1H), 7.48 (d, 2H), 7.58 (d, 2H), 7.82 (1H), 7.89 (d, 1H), 8.79 (s, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe formed mixture was concentrated
  3. customto afford an oil which
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic layer was concentrated
  6. customto afford an oil which
  7. customwas purified by preparative TLC and preparative HPLC

Sources & evidence

ORD record
ord-ed795a19422342f5a7a02f2580efa17a
Source dataset
uspto-grants-2015_01
Patent number
US08933072B2

Reaction notes

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