Azidotrimethylsilane → HCID 59459380, compound

HRID 238761Notes

Reaction equation

HRID 238761 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][NH:8][C:9]([NH:11][C@@:12]([C:27]1[CH:32]=[C:31]([O:33][C:34]([F:39])([F:38])[CH:35]([F:37])[F:36])[CH:30]=[C:29]([F:40])[CH:28]=1)([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])#[N:2].[Si]([N:45]=[N+:46]=[N-:47])(C)(C)C>COCCOC>[N:2]1[NH:45][N:46]=[N:47][C:1]=1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][NH:8][C:9]([NH:11][C@@:12]([C:27]1[CH:32]=[C:31]([O:33][C:34]([F:38])([F:39])[CH:35]([F:36])[F:37])[CH:30]=[C:29]([F:40])[CH:28]=1)([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:10]

Participants

4

Reactant 2

HCID 78378Azidotrimethylsilane2×HCID 59458832HCID 59458832, compound

Product 1

HCID 59459380HCID 59459380, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (R)-1-(5-cyanopentyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea, prepared by the method described in Procedure 12 (45 mg, 0.080 mmol) in DME (161 μL) at rt was added TMSN3 (0.013 mL, 0.16 mmol), followed by n-Bu2SnO2 (2 mg, 0.008 mmol). The reaction mixture was heated at 150° C. for 10 min under microwave irradiation. An additional amount of TMSN3 (0.013 mL, 0.16 mmol) and n-Bu2SnO2 (2 mg, 0.008 mmol) was added, and the reaction mixture was heated at 150° C. for an additional 10 min under microwave irradiation. The reaction mixture was concentrated and the residue was dissolved in MeOH and purified by preparative HPLC (Phenoma Luna AXIA 10A, C18, eluting with MeCN/H2O containing 0.1% TFA, monitoring at 220 nm) to provide (R)-1-(5-(2H-tetrazol-5-yl)pentyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea (23 mg, 47% yield) as a white solid. 1H NMR (500 MHz, MeOH-d4) δ 7.18-6.89 (m, 11H), 6.71 (d, J=5 Hz, 2H), 6.37-6.16 (m, 1H), 3.93 (d, J=15 Hz, 1H), 3.81 (d, J=15.0 Hz, 1H), 3.08 (t, J=5 Hz, 2H), 2.94 (t, J=5 Hz, 2H), 1.83-1.76 (m, 2H), 1.55-1.48 (m, 2H), 1.41-1.35 (m, 2H); LC/MS: RT=3.736 min [M+H] 607.3 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeCN/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm).

Workup

  1. temperaturethe reaction mixture was heated at 150° C. for an additional 10 min under microwave irradiation
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in MeOH
  4. custompurified by preparative HPLC (Phenoma Luna AXIA 10A, C18, eluting with MeCN/H2O containing 0.1% TFA, monitoring at 220 nm)

Sources & evidence

ORD record
ord-e15b55112e6044c1a9f04a54c339db89
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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