Diisopropylethylamine → HCID 58498865, compound

HRID 1471187Notes

Reaction equation

HRID 1471187 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][Si:26]([C:29]#[C:30][C:31]1[NH:35][C:34]([C@@H:36]2[CH2:41][C@@H:40]3[C@@H:38]([CH2:39]3)[NH:37]2)=[N:33][CH:32]=1)([CH3:28])[CH3:27].[CH3:42][O:43][C:44]([NH:46][C@@H:47]([CH:51]([CH3:53])[CH3:52])[C:48](O)=[O:49])=[O:45].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:52][CH:51]([CH3:53])[C@H:47]([NH:46][C:44](=[O:45])[O:43][CH3:42])[C:48](=[O:49])[N:37]1[C@H:36]([C:34]2[NH:35][C:31]([C:30]#[C:29][Si:26]([CH3:27])([CH3:28])[CH3:25])=[CH:32][N:33]=2)[CH2:41][C@@H:40]2[C@H:38]1[CH2:39]2

Participants

6

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 58498682HCID 58498682, compound

Product 1

HCID 58498865HCID 58498865, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (428 mg, 1.125 mmol) was added to a stirred solution of (1R,3S,5R)-3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (212 mg, 0.865 mmol) and (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (197 mg, 1.125 mmol) in DMF (3 mL) and DIPEA (1.2 mL, 6.9 mmol) and the reaction was stirred at rt overnight. The reaction was concentrated to dryness and then purified with a BIOTAGE® Horizon (25 g SiO2, 40-60% EtOAc/hexanes) to yield methyl(S)-3-methyl-1-oxo-1-((1R,3S,5R)-3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)butan-2-ylcarbamate (203 mg) as a yellow glass. LC-MS retention time 3.095 min; m/z 403.29 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) δ ppm 7.17 (br. s., 1 H), 5.04-5.11 (m, 1 H), 4.54 (d, J=6.8 Hz, 1 H), 3.65 (s, 3 H), 3.54-3.61 (m, 1 H), 2.82 (s, 1 H), 2.39-2.50 (m, 1 H), 2.27-2.36 (m, 1 H), 2.04-2.15 (m, 1 H), 1.94-2.04 (m, 1 H), 1.11 (dt, J=8.7, 5.6 Hz, 1 H), 0.95 (d, J=6.8 Hz, 3 H), 0.90 (d, J=6.8 Hz, 3 H), 0.73-0.79 (m, 1 H), 0.21 (s, 9 H).

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. custompurified with a BIOTAGE® Horizon (25 g SiO2, 40-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d94c8b7a5fbe4771bc39fb66c73a103d
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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