Water → HCID 59225636, compound

HRID 1426138Notes

Reaction equation

HRID 1426138 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:16][C:17]2[S:18][CH:19]=[C:20]([CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])[N:21]=2)=[N:11][CH:12]=[C:13](Br)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28](B1C2CCCC1CCC2)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH2:28]([C:13]1[N:14]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:10]([NH:16][C:17]2[S:18][CH:19]=[C:20]([CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])[N:21]=2)=[N:11][CH:12]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 962WaterHCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonaneHCID 59225686HCID 59225686, compound

Product 1

HCID 59225636HCID 59225636, compoundYield 78.8%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Methyl 3-(2-(3-(benzyloxy)-5-bromopyrazin-2-ylamino)thiazol-4-yl)propanoate (0.826 g, 1.84 mmol), 9-benzyl-9-bora-bicyclo[3.3.1]nonane (11.0 mL, 5.51 mmol), PdCl2(dppf) dichloromethane adduct (0.151 g, 0.184 mmol), were placed in DMF (25 mL), and water (2.5 mL) and heated to 60° C. for 90 minutes. Cooled reaction mixture to room temperature and partitioned between water and DCM. Layers were separated, dried, filtered, and concentrated. Purified by silica gel to give methyl 3-(2-(5-benzyl-3-(benzyloxy)pyrazin-2-ylamino)thiazol-4-yl)propanoate (0.667 g, 78.8% yield). 28 mg of this was dissolved in DCM and 2M HCl was added and concentrated to give methyl 3-(2-(5-benzyl-3-(benzyloxy)pyrazin-2-ylamino)thiazol-4-yl)propanoate hydrochloride (0.027 g, 93%) 1H NMR (DMSO-d6) δ 7.79 (s, 1H), 7.52 (m, 2H), 7.32 (m, 4H), 7.27 (d, 4H), 7.20 (m, 1H), 5.44 (s, 2H), 3.93 (s, 2H), 3.60 (s, 3H), 2.86 (m, 2H), 2.68 (m, 2H). Mass spectrum (apci) m/z=461.1.0 (M+H-HCl).

Workup

  1. temperatureCooled
  2. customreaction mixture to room temperature
  3. custompartitioned between water and DCM
  4. customLayers were separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurified by silica gel

Sources & evidence

ORD record
ord-eae6b8567d214826861e56df9967a8ad
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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