Methanol → HCID 53232761, compound

HRID 1891486Notes

Reaction equation

HRID 1891486 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:17][C:16]([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:15][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[S:17][C:16]([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:15][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 58367180HCID 58367180, compound

Product 1

HCID 53232761HCID 53232761, compoundYield 61.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Prepared using General Procedure 17: To a stirred solution of (R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate (13 mg, 0.02 mmol) in THF (0.5 mL) was added sodium borohydride (2.3 mg, 0.06 mmol) at room temperature. The reaction was heated to 75° C. and methanol (0.03 mL, 0.7 mmol) was added dropwise. After 1 h, the reaction was cooled and concentrated. Purification of the crude material by preparative HPLC gave 6 mg (60%) of (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide 46. LCMS-ESI (m/z) calculated for C23H24N4O4S2: 484.1; found 485.1 [M+H]+, tR=3.26 min. 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J=8.9, 2.3 Hz, 1H), 8.16 (d, J=2.3 Hz, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.43 (t, J=7.6 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 5.19-4.96 (m, 1H), 4.87-4.63 (m, 3H), 4.17 (dd, J=8.2, 4.4 Hz, 2H), 3.53 (ddd, J=17.2, 8.8, 3.5 Hz, 1H), 3.46-3.34 (m, 2H), 3.32-3.11 (m, 1H), 2.86-2.59 (m, 1H), 2.19-1.97 (m, 1H), 1.48 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 166.83, 165.72, 161.71, 144.11, 141.85, 133.47, 133.26, 129.53, 127.99, 126.92, 126.58, 122.64, 115.51, 113.87, 103.79, 72.54, 58.86, 57.43, 55.67, 34.69, 31.27, 21.73. Chiral HPLC: (R)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyethanesulfonamide was eluted in MeOH, 96.2% ee, tR=12.58 min (Chiral Method 2).

Workup

  1. customPrepared
  2. temperaturethe reaction was cooled
  3. concentrationconcentrated
  4. customPurification of the crude material by preparative HPLC

Sources & evidence

ORD record
ord-bd06baeec8fc45aeb93bb9428c7fb71e
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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