Diisopropylethylamine → HCID 178517966, compound

HRID 1641306Notes

Reaction equation

HRID 1641306 reaction equation
Cl.Cl.[CH:3]1([NH:9][C:10]2[C:14]3([CH2:19][CH2:18][NH2+:17][CH2:16][CH2:15]3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[CH:28]([C:30]1[CH:31]=[C:32]([B:36]([OH:38])[OH:37])[CH:33]=[CH:34][CH:35]=1)=O.CCN(C(C)C)C(C)C.C([BH3-])#N>C1COCC1.CC(O)=O>[CH:3]1([NH:9][C:10]2[C:14]3([CH2:15][CH2:16][N:17]([CH2:28][C:30]4[CH:31]=[C:32]([B:36]([OH:38])[OH:37])[CH:33]=[CH:34][CH:35]=4)[CH2:18][CH2:19]3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 498716Cyano-borohydrideHCID 27343563-Formylphenylboronic acidHCID 178478874HCID 178478874, compound

Product 1

HCID 178517966HCID 178517966, compound

Reagents, catalysts & solvents 1

HCID 23444217Acetic acid tetrahydrofuranSolvent

Procedure

To a solution of 3.0 g (7.188 mmol) 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dihydrochloride in 30 mL THF:AcOH (9:1) was added 1.8 g (12.005 mmol) 3-formylphenylboronic acid and 5.53 g (21.567 mmol) PS-DIEA resin and 5.97 g (14.388 mmol) MP-cyanoborohydride resin. The heterogeneous reaction mixture was stirred at rt for 24 hrs, then filtered, washed with 100 mL methanol, and concentrated. Purification by automated flash chromatography (8-30% CH3CN/H2O over 41 min, 0.05% added TFA reverse phase YMC ODSA 120 Å, 15-30 μM particle size,) afforded 3-{[4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-en-8-yl]methyl}phenylboronic acid as a solid. 1H NMR (CD3OD, 400 MHz) δ 7.44 (m, 1H), 7.38 (d, J=7.32 Hz, 1H), 7.29 (s, 1H), 7.18 (m, 1H), 7.09 (m, 3H) 6.93 (m, 1H), 3.75 (m, 1H), 3.31 (s, 2H), 2.78 (m, 2H), 2.12 (m, 4H), 1.97 (m, 4H), 1.78 (m, 2H), 1.65 (m, 1H), 1.35 (m, 5H). High resolution mass spec (FT/ICR) calc M+H=478.2661 found 478.2709.

Workup

  1. filtrationfiltered
  2. washwashed with 100 mL methanol
  3. concentrationconcentrated
  4. customPurification
  5. additionby automated flash chromatography (8-30% CH3CN/H2O over 41 min, 0.05% added TFA reverse phase YMC ODSA 120 Å, 15-30 μM particle size,)

Sources & evidence

ORD record
ord-ddde16c1dc7e4cd485c23c1b8d84d8e4
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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