Methylamine → HCID 86670469, compound

HRID 1911853Notes

Reaction equation

HRID 1911853 reaction equation
CN.[C:3]([O:7][C:8]([N:10]1[C@@H:14]([C@H:15]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:13][CH2:12][C@H:11]1[CH2:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:40][N:41](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.C1COCC1>[Si:23]([O:22][C@H:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@H:14]1[CH2:13][CH2:12][C@@H:11]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([C:35](=[O:36])[NH:41][CH3:40])=[CH:38][CH:39]=2)[N:10]1[C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])([C:26]([CH3:28])([CH3:29])[CH3:27])([CH3:24])[CH3:25]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67971935HCID 67971935, compound

Product 1

HCID 86670469HCID 86670469, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methylamine (5.71 mL of a 2M THF solution, 11.4 mmol) was added to a stirred, room temperature solution of 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid (2.00 g, 3.80 mmol), HATU (1.736 g, 4.56 mmol, 1.2 equivalents) and DIPEA (3.32 mL, 19.0 mmol, 5 equivalents) in DMF (7.8 mL). The reaction was stirred at room temperature for 12 hours, after which the mixture was diluted with EtOAc and partitioned with water. The aqueous layer was extracted with EtOAc (3×), and the combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by normal phase flash chromatography using silica gel (0-50% hexanes/ethyl acetate). The product fractions were collected and concentrated in vacuo to afford the title compound as a white solid (1.20 g, 59%). LC-MS=561.2 (M+Na)+.

Workup

  1. custompartitioned with water
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by normal phase flash chromatography
  8. customThe product fractions were collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-484b98469d50470895a1e58bba4d9704
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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