Water → HCID 70652049, compound

HRID 1528662Notes

Reaction equation

HRID 1528662 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([NH2:13])=[O:12])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[OH:20][C:21]([CH3:54])([CH3:53])[CH2:22][C@:23]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:28][CH2:27][N:26]([C@H:29]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)[CH3:30])[C:25](=[O:46])[NH:24]1.O>C(O)C.C1(C)C=CC=CC=1.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>[OH:20][C:21]([CH3:53])([CH3:54])[CH2:22][C@:23]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:28][CH2:27][N:26]([C@H:29]([C:31]2[CH:32]=[CH:33][C:34]([C:2]3[CH:3]=[CH:4][C:5]([C:8]4([C:11]([NH2:13])=[O:12])[CH2:10][CH2:9]4)=[N:6][CH:7]=3)=[CH:35][CH:36]=2)[CH3:30])[C:25](=[O:46])[NH:24]1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 59627210HCID 59627210, compoundHCID 67996687HCID 67996687, compound

Product 1

HCID 70652049HCID 70652049, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1-(5-Bromo-pyridin-2-yl)-cyclopropanecarboxylic acid amide (120 mg), Na2CO3 (443 mg), and Pd(PPh3)4 (12 mg) were added to a solution of (S)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}tetrahydro-pyrimidin-2(1H)-one (200 mg; for preparation see WO 2009061498) in ethanol (6 mL), toluene (8 mL), and H2O (4 mL) at room temperature. The resulting mixture was stirred at 100° C. for 2 h under N2 atmosphere. After cooling to room temperature, the mixture was concentrated, diluted with H2O (30 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers were concentrated to afford an oil which was purified by preparative HPLC to give the title compound. Yield: 124 mg (58% of theory); LC (method 4): tR=0.98 min; Mass spectrum (ESI+): m/z=513 [M+H]+; 1H NMR (CDCl3, 400 MHz) δ 0.69 (s, 3H), 1.29 (m, 2H), 1.31 (m, 3H), 1.50 (d, 3H), 1.79 (m, 2H), 1.98-2.07 (m, 3H), 2.12-2.22 (m, 3H), 2.70-2.83 (m, 1H), 4.55 (s, 1H), 5.80-5.62 (m, 2H), 7.21 (m, 3H), 7.28 (m, 1H), 7.33 (m, 4H), 7.70 (m, 2H), 7.78 (m, 1H) 8.69 (s, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe mixture was concentrated
  3. additiondiluted with H2O (30 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic layers were concentrated
  6. customto afford an oil which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-81eb01c0ed5a4585a47a8794d5ccbf72
Source dataset
uspto-grants-2015_07
Patent number
US09090605B2

Reaction notes

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