Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1) → HCID 70216569, compound

HRID 2047212Notes

Reaction equation

HRID 2047212 reaction equation
[CH3:1][Si:2]([CH3:52])([CH3:51])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH2:28][N:29]([C:37]2([CH2:40][OH:41])[CH2:39][CH2:38]2)[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:9]=1[Br:42].F[B-](F)(F)F.[CH3:58][O+](C)C>C(Cl)Cl>[CH3:52][Si:2]([CH3:1])([CH3:51])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:49])([CH3:48])[CH3:50])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH2:28][N:29]([C:37]2([CH2:40][O:41][CH3:58])[CH2:39][CH2:38]2)[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:9]=1[Br:42]

Participants

4

Reactant 2

HCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 68074440HCID 68074440, compound

Product 1

HCID 70216569HCID 70216569, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To tert-butyl (7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl(1-(hydroxymethyl)cyclopropyl)carbamate (0.19 g, 0.23 mmol) in DCM (2.5 ml) was added protonsponge (70 mg, 0.33 mmol) followed by trimethyloxoniumtetrafluoroborate (48.2 mg, 0.33 mmol) at room temperature and the resulting mixture was stirred at room temperature for 16 h, at which time LC/MS confirmed full conversion of starting material to product. Reaction mixture was quenched with sat. NH4Cl and diluted with DCM (25 ml). Organics were separated and washed with brine (5 ml) and dried over MgSO4. Solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. Elution with DCM/MeOH (0-50%) gave slightly impure desired tert-butyl (7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl(1-(methoxymethyl)cyclopropyl)carbamate (97 mg, 50%).

Workup

  1. customReaction mixture
  2. customwas quenched with sat. NH4Cl
  3. additiondiluted with DCM (25 ml)
  4. customOrganics were separated
  5. washwashed with brine (5 ml)
  6. dry with materialdried over MgSO4
  7. customSolvent was removed in vacuo
  8. customthe residue was purified by column chromatography on silica gel
  9. washElution with DCM/MeOH (0-50%)

Sources & evidence

ORD record
ord-dc70ac25974a4d9ea97075e5c519e27a
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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