Isopropyl chloroformate → HCID 57947900, compound

HRID 340911Notes

Reaction equation

HRID 340911 reaction equation
[F:1][C:2]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:3]=1[CH2:4][NH:5][C:6](=[O:31])[N:7]([C@H:9]([CH2:16][O:17][C:18](=[O:30])[NH:19][C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:10][CH2:11][CH2:12][C:13](O)=[O:14])[CH3:8].C(N(CC)CC)C.ClC(OC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[CH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:29]=[C:20]([NH:19][C:18](=[O:30])[O:17][CH2:16][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]2[CH:32]=[CH:33][CH:34]=[C:35]([F:36])[C:2]=2[F:1])=[O:31])[CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[N:21]=1

Participants

7

Reactant 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 57947387HCID 57947387, compound

Product 1

HCID 57947900HCID 57947900, compoundYield 58.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-5-(3-(2,3-difluorobenzyl)-1-methylureido)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoic acid (˜2.04 mmol, 1.0 equiv.) and triethylamine (0.38 mL, 2.78 mmol, 1.2 equiv.) in anhydrous THF (7 mL) was added isopropyl chloroformate (2.80 mL, 2.80 mmol, 1.2 equiv.) dropwise at 0° C. After stirred at RT for 20 min, the mixture was filtered and transferred to a solution of NaBH4 (0.18 g, 4.76 mmol, 2.0 equiv.) in water (2.0 mL). The resulting mixture was stirred at RT for 1 h, and quenched with saturated NH4Cl. The solution was extracted with EtOAC twice. The organic layers were washed with brine, dried over Na2SO4, and concentrated. The resulting residue was purified on silica gel column (50-100% EtOAc in hexanes followed by 10% MeOH in dichloromethane) to give (S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-6-hydroxyhexyl isoquinolin-3-ylcarbamate (0.58 g, 52% for two steps). LRMS (M+H+) m/z 487.3.

Workup

  1. filtrationthe mixture was filtered
  2. stirringThe resulting mixture was stirred at RT for 1 h
  3. customquenched with saturated NH4Cl
  4. extractionThe solution was extracted with EtOAC twice
  5. washThe organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe resulting residue was purified on silica gel column (50-100% EtOAc in hexanes followed by 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-df454af5c7ac44729a4d0910d0b3d822
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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