Sodium borohydride → HCID 58344683, compound

HRID 1809502Notes

Reaction equation

HRID 1809502 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@@H:22]4[NH:27][C@@H:28]([CH3:33])[C:29](OC)=[O:30])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[BH4-].[Na+]>CO.Cl>[OH:30][CH2:29][C@@H:28]([NH:27][C@@H:22]1[C:23]2[C:19](=[C:18]([C:15]3[N:14]=[C:13]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:12])[CH3:11])=[C:3]([CH:4]=4)[C:1]#[N:2])[O:17][N:16]=3)[CH:26]=[CH:25][CH:24]=2)[CH2:20][CH2:21]1)[CH3:33]

Participants

5

Reactant 2

HCID 4311764Sodium borohydride2×HCID 67195340HCID 67195340, compound

Product 1

HCID 58344683HCID 58344683, compoundYield 41.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of (S)-methyl 2-(((S)-4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)amino)propanoate (33 mg, 0.07 mmol) in MeOH (2 mL) at 0° C. was added NaBH4 (14 mg, 0.4 mmol). The reaction was allowed to warm to room temperature after 1 h. Incremental amounts of NaBH4 (˜10-15 mg each) were added at 1 h intervals until LC/MS indicated >80% conversion to product. The reaction mixture was diluted with 1N HCl and extracted with DCM (2×). The combined organic layers were dried over Na2SO4 and concentrated. The resulting crude solid was dissolved in DCM and chromatographed (MeOH/DCM) to provide 12.1 mg (40%) of 5-(3-((S)-1-(((S)-1-hydroxypropan-2-yl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadia-zol-5-yl)-2-isopropoxybenzonitrile 53. LCMS-ESI (m/z) calculated for C25H26N4O4: 418.5; found 419.1 [M+H]+, tR=2.56 min. 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J=2.2 Hz, 1H), 8.14 (dd, J=8.9, 2.2 Hz, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.28 (d, J=7.5 Hz, 1H), 7.19 (t, J=7.6 Hz, 1H), 6.92 (d, J=9.1 Hz, 1H), 4.69-4.51 (m, 1H), 4.21 (m, 1H), 3.43 (m, 1H), 3.37-3.19 (m, 1H), 3.10 (m, 2H), 2.95-2.78 (m, 1H), 2.46 (dd, J=6.5, 4.6 Hz, 1H), 2.34-2.17 (m, 1H), 1.81-1.65 (m, 1H), 1.28 (d, J=6.1 Hz, 6H), 0.98 (d, J=6.4 Hz, 3H). Chiral HPLC eluting with 10% IPA/hexanes, plus 0.3% TEA, tR=13.72 min.

Workup

  1. extractionextracted with DCM (2×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. dissolutionThe resulting crude solid was dissolved in DCM
  5. customchromatographed (MeOH/DCM)

Sources & evidence

ORD record
ord-0abc6caa4f11423594580a9c568e02a3
Source dataset
uspto-grants-2013_01
Patent number
US08362048B2

Reaction notes

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