Methanol → HCID 67194420, compound

HRID 1051087Notes

Reaction equation

HRID 1051087 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][S:28]([CH2:31][C:32](OC)=[O:33])(=[O:30])=[O:29])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[BH4-].[Na+].CO>C1COCC1>[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][S:28]([CH2:31][CH2:32][OH:33])(=[O:29])=[O:30])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 67198242HCID 67198242, compound

Product 1

HCID 67194420HCID 67194420, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Prepared using General Procedure 18: To a stirred solution of (R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate (0.72 g, 1.5 mmol) in THF (25 mL) was added sodium borohydride (0.24 g, 6.2 mmol) at room temperature. The reaction was heated to 75° C. and methanol (0.06 mL, 1.5 mmol) was added dropwise. After 1 h, the reaction was cooled and concentrated. The residue was partitioned between DCM and 0.5N HCl. The organic layer was dried over MgSO4, concentrated, and recrystallized from methanol to give 0.40 g (60%) of (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide 186. LCMS-ESI (m/z) calculated for C23H24N4O5S: 468.2. found 491.1 [M+Na]+, tR=8.64 min (Method 2). Elemental Analysis determined for C23H24N4O5S; C calculated=58.96%. found=58.86%; H calculated=5.16%. found=5.08%; N calculated=11.96%. found=11.78%. 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 8.10 (d, J=7.7 Hz, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.42 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.1 Hz, 1H), 5.05 (q, J=7.9 Hz, 1H), 4.94-4.69 (m, 2H), 4.30-3.91 (m, 2H), 3.49 (ddd, J=17.4, 8.8, 3.5 Hz, 1H), 3.39 (td, J=4.8, 1.6 Hz, 2H), 3.25-3.07 (m, 1H), 2.71 (dtd, J=11.5, 8.0, 3.6 Hz, 1H), 2.11-1.95 (m, 1H), 1.48 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 173.30, 168.79, 162.95, 143.72, 142.80, 134.25, 134.04, 129.06, 127.76, 127.23, 123.52, 116.84, 115.41, 113.72, 104.06, 72.94, 59.01, 57.56, 55.84, 34.85, 31.61, 21.88. Chiral HPLC: (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide was eluted with methanol (Chiral Method 2): 99.9% ee, tR=8.59 min. (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide 187 was synthesized in an analogous fashion from (S)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate: >99.9% ee, tR for (S)-enantiomer=6.62 min (Chiral Method 2).

Workup

  1. customPrepared
  2. temperaturethe reaction was cooled
  3. concentrationconcentrated
  4. customThe residue was partitioned between DCM and 0.5N HCl
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customrecrystallized from methanol

Sources & evidence

ORD record
ord-069a406850b548a3b58b4ad856224669
Source dataset
uspto-grants-2016_07
Patent number
US09388147B2

Reaction notes

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