Diisopropylethylamine → HCID 86670471, compound

HRID 1911855Notes

Reaction equation

HRID 1911855 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH2:8][NH:9][CH3:10])[CH:5]=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([N:18]1[C@@H:22]([C@H:23]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:21][CH2:20][C@H:19]1[CH2:38][C:39]1[CH:47]=[CH:46][C:42]([C:43](O)=[O:44])=[CH:41][CH:40]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12].CN(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>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]([CH3:10])[C:43]([C:42]2[CH:41]=[CH:40][C:39]([CH2:38][C@H:19]3[CH2:20][CH2:21][C@@H:22]([C@H:23]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:18]3[C:16]([O:15][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:17])=[CH:47][CH:46]=2)=[O:44])[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 185259431-(6-Bromopyridin-2-yl)-N-methylmethanamineHCID 67971935HCID 67971935, compound

Product 1

HCID 86670471HCID 86670471, compoundYield 27.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(6-Bromopyridin-2-yl)-N-methylmethanamine (115 mg, 0.571 mmol) was added to a stirred, room temperature mixture of 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid (300 mg, 0.571 mmol), HATU (260 mg, 0.685 mmol, 1.2 equivalents) and DIPEA (498 μL, 2.85 mmol, 5 equivalents) in DMF (2.8 mL). The reaction was stirred at room temperature for 12 hours, and then diluted with EtOAc and partitioned with water. The aqueous layer was extracted with EtOAc (3×), and the combined organic extracts 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 was collected and concentrated in vacuo to afford the title compound (110 mg, 27%). LC-MS=608.2 & 610.2 (M-Boc+H)+.

Workup

  1. custompartitioned with water
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washthe combined organic extracts 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 was collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0d49005e37394ea0b8f9ffafacef9e2b
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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