Sodium borohydride → N-(2-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-2-oxoethyl)-2-(5-(hydroxymethyl)thiazol-2-ylamino)-3-methylbutanamide

HRID 1755449Notes

Reaction equation

HRID 1755449 reaction equation
[NH2:1][C:2](=[O:31])[C@@H:3]([NH:12][C:13](=[O:30])[CH2:14][NH:15][C:16](=[O:29])[CH:17]([NH:21][C:22]1[S:23][C:24]([CH:27]=[O:28])=[CH:25][N:26]=1)[CH:18]([CH3:20])[CH3:19])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[BH4-].[Na+]>CCO.O>[NH2:1][C:2](=[O:31])[C@@H:3]([NH:12][C:13](=[O:30])[CH2:14][NH:15][C:16](=[O:29])[CH:17]([NH:21][C:22]1[S:23][C:24]([CH2:27][OH:28])=[CH:25][N:26]=1)[CH:18]([CH3:19])[CH3:20])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([OH:11])=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86700099N-(2-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-2-oxoethyl)-2-(5-formylthiazol-2-ylamino)-3-methylbutanamide

Product 1

HCID 86700098N-(2-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-2-oxoethyl)-2-(5-(hydroxymethyl)thiazol-2-ylamino)-3-methylbutanamide

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

To a solution of material from Example 31 in EtOH/H2O (4:1) (2.5 mL) is added sodium borohydride (25.5 mg, 0.674 mmol) in 2 equal portions over 5 min. The resulting light suspension is stirred at room temp for 2 h, quenched with MeOH (3 mL), stirred at room temp for 30 min, quenched with acetone (5 mL), and stirred at room temp for 45 min. All volatiles were evaporated off under a gentle stream of N2 to give the title compound (quantitative yield) that is used in its entirety in the macrocyclization step. LC/MS (Condition A): ret. T=1.45 min, (M+H)+ 450.20.

Workup

  1. customquenched with MeOH (3 mL)
  2. stirringstirred at room temp for 30 min
  3. customquenched with acetone (5 mL)
  4. stirringstirred at room temp for 45 min
  5. customAll volatiles were evaporated off under a gentle stream of N2

Sources & evidence

ORD record
ord-9af9ebc238734731bec169b762fbf9d5
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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