Ammonium Chloride → HCID 53465995, compound

HRID 626091Notes

Reaction equation

HRID 626091 reaction equation
[OH:1][C@H:2]([CH2:24][N:25]([CH2:37][CH:38]([CH3:40])[CH3:39])[S:26]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)(=[O:28])=[O:27])[C@@H:3]([NH:11][C:12](=[O:23])[O:13][C@H:14]1[CH2:22][C@H:17]2[O:18][CH2:19][C:20](=[O:21])[C@H:16]2[CH2:15]1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[BH4-].[Na+].[NH4+].[Cl-]>CCO>[OH:1][C@H:2]([CH2:24][N:25]([CH2:37][CH:38]([CH3:40])[CH3:39])[S:26]([C:29]1[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=1)(=[O:28])=[O:27])[C@@H:3]([NH:11][C:12](=[O:23])[O:13][C@H:14]1[CH2:22][C@H:17]2[O:18][CH2:19][C@@H:20]([OH:21])[C@H:16]2[CH2:15]1)[CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 53465994HCID 53465994, compound

Product 1

HCID 53465995HCID 53465995, compoundYield 81.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of keto-inhibitor 19a (10 mg, 17 μmol) in EtOH was cooled to −25° C. and NaBH4 (6 mg) was added at once. The solution was stirred for 30 min then saturated NH4Cl aq. solution was added. The aqueous phase was extracted with EtOAc (4×), the combined organic layer was dried, filtered and evaporated. The residue was purified by column chromatography on silica gel using hexanes:EtOAc (2:1, 1:1, then 1:2) as the eluent to afford the desired inhibitor 22 (8 mg, 80%). TLC: Rf=0.22 (hexanes/EtOAc=1:2); 1H NMR (CDCl3, 400 MHz) δ 7.70 (d, J=8.8 Hz, 1H), 7.32-7.17 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 5.07 (m, 1H), 4.96 (d, J=7.2 Hz, 1H), 4.38 (, t, J=6.8 Hz, 1H), 4.22 (m, 1H), 3.87 (s, 3H), 3.88-3.74 (m, 3H), 3.54 (dd, J=3.2, 9.6 Hz, 1H), 3.10 (dd, J=7.8, 15.0 Hz, 1H), 3.05-2.82 (m, 4H), 2.78 (dd, J=6.8, 13.6 Hz, 1H), 2.42 (dd, J=10.8 Hz, 1H), 2.18-2.04 (m, 2H), 1.94-1.76 (m, 3H); TLC: Rf=0.39 (hexanes/EtOAc=1:5); 1H NMR (CDCl3, 500 MHz) δ 7.70 (d, J=8.8 Hz, 2H), 7.32-7.19 (m, 5H), 6.97 (d, J=8.8 Hz, 2H), 5.07 (m, 1H), 4.89 (d, J=7.2 Hz, 1H), 4.38 (t, J=6.8 Hz, 1H), 4.21 (m, 1H), 3.87 (s, 3H), 3.88-3.74 (m, 4H), 3.54 (dd, J=3.2, 9.6 Hz, 1H), 3.10 (dd, J=7.8, 15.0 Hz, 1H), 3.05-2.82 (m, 5H), 2.78 (dd, J=6.8, 13.4 Hz, 1H), 2.42 (br.s, 1H), 2.18-2.04 (m, 2H), 1.94-1.76 (m, 3H), 0.90 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ 163.0, 155.3, 137.6, 129.9, 129.6, 129.5, 128.6, 126.5, 114.3, 84.9, 78.1, 76.3, 73.0, 72.2, 58.7, 55.6, 55.3, 53.7, 47.3, 39.1, 35.4, 31.3, 27.2, 20.1, 19.9; HRMS-ESI (m/z): [M+Na+] calcd for C30H42N2O2SNa 597.2610. found 597.2608.

Workup

  1. extractionThe aqueous phase was extracted with EtOAc (4×)
  2. customthe combined organic layer was dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-cd9e5b7d74aa47329423359da353e0b4
Source dataset
uspto-grants-2016_04
Patent number
US09309213B2

Reaction notes

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