Methyl N-(triethylammoniosulfonyl)carbamate → HCID 59608329, compound

HRID 1469613Notes

Reaction equation

HRID 1469613 reaction equation
C([O:8][C:9](=[O:40])[C@H:10]([CH3:39])[CH2:11][C@H:12]([NH:26][C:27](=[O:38])[C:28](=[O:37])[NH:29][NH:30][C:31](=O)[C:32]([F:35])([F:34])[F:33])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:16][CH:15]=1)C1C=CC=CC=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:18]=[CH:19][C:14]([CH2:13][C@@H:12]([NH:26][C:27]([C:28]2[O:37][C:31]([C:32]([F:34])([F:35])[F:33])=[N:30][N:29]=2)=[O:38])[CH2:11][C@@H:10]([CH3:39])[C:9]([OH:8])=[O:40])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 59608189HCID 59608189, compound

Product 1

HCID 59608329HCID 59608329, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R,4S)-5-biphenyl-4-yl-2-methyl-4-{2-oxo-2-[N′-(2,2,2-trifluoro-acetyl)-hydrazino]-acetylamino}-pentanoic acid benzyl ester (177 mg, 0.319 mmol) in THF (10 mL) at room temperature is added Burgess reagent (304 mg, 1.274 mmol). The reaction is carried out in a microwave at 130° C. for 30 minutes. The reaction is quenched by brine and is extracted with ethyl acetate. The combined organic layer is concentrated and purified by reverse phase HPLC [70% to 85% acetonitrile-H2O (containing 0.1% TFA)] to give the benzyl ester of the title compound. The obtained benzyl ester intermediate is dissolved in MeOH (4 mL) and is hydrogenated with 10% Pd/C at room temperature for 20 minutes. The reaction mixture is purified by reverse phase HPLC [45% to 70% acetonitrile-H2O (containing 0.1% TFA)] to give (2R,4S)-5-biphenyl-4-yl-2-methyl-4-[(5-trifluoromethyl-[1,3,4]oxadiazole-2-carbonyl)-amino]-pentanoic acid. HPLC Retention time 1.38 minutes (condition D); MS 448 (M+1); 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (d, J=7.3 Hz, 3 H), 1.60-1.71 (m, 1 H), 1.84-1.95 (m, 1 H), 2.41-2.49 (m, 1 H), 2.80-2.88 (m, J=13.9, 6.1 Hz, 1 H), 2.92 (dd, J=13.6, 7.8 Hz, 1 H), 4.21-4.34 (m, 1 H), 7.27-7.37 (m, 3 H), 7.44 (t, J=7.7 Hz, 2 H), 7.58 (d, J=8.3 Hz, 2 H), 7.61-7.66 (m, 2 H), 9.50 (d, J=8.8 Hz, 1 H), 12.05 (br. s., 1 H).

Workup

  1. customThe reaction is quenched by brine
  2. extractionis extracted with ethyl acetate
  3. concentrationThe combined organic layer is concentrated
  4. custompurified by reverse phase HPLC [70% to 85% acetonitrile-H2O (containing 0.1% TFA)]

Sources & evidence

ORD record
ord-75255d9df5474e45ae4c3a6b4a6d95dd
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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