Sulfamide → HCID 53232873, compound

HRID 1891488Notes

Reaction equation

HRID 1891488 reaction equation
Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[S:29](N)([NH2:32])(=[O:31])=[O:30]>O1CCOCC1>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[S:16][C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][S:29]([NH2:32])(=[O:31])=[O:30])=[N:13][N:14]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

4

Reactant 2

HCID 82267SulfamideHCID 67193845(S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride

Product 1

HCID 53232873HCID 53232873, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Prepared using General Procedure 18: To (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (25 mg, 0.06 mmol) in dioxane (1 mL) was added sulfamide (30 mg, 0.3 mmol) and the mixture was heated to 90° C. After 16 h, the solvent was evaporated and the residue was purified by column chromatography. Additional purification by recrystallization from MeOH provided 15.9 mg (26%) of (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamide 47. LCMS-ESI (m/z) calculated for C21H21N5O3S2: 455.1; found 456.1 [M+H]+, tR=3.33 min. 1H NMR (400 MHz, DMSO) δ 8.40 (d, J=2.3 Hz, 1H), 8.32 (dd, J=8.9, 2.4 Hz, 1H), 7.88 (d, J=7.7 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.56-7.38 (m, 2H), 7.23 (d, J=9.0 Hz, 1H), 6.75 (s, 2H), 4.95 (dt, J=12.2, 6.1 Hz, 1H), 4.87 (dd, J=16.6, 8.2 Hz, 1H), 3.42-3.26 (m, 1H), 3.07 (dt, J=16.4, 8.3 Hz, 1H), 2.61 (dtd, J=11.0, 7.9, 3.0 Hz, 1H), 2.00 (dq, J=12.7, 8.8 Hz, 1H), 1.38 (d, J=6.0 Hz, 6H). 13C NMR (101 MHz, DMSO) δ 166.64, 165.62, 161.19, 146.08, 141.36, 133.89, 133.15, 127.97, 127.51, 127.27, 125.78, 122.22, 115.57, 114.95, 102.29, 72.17, 57.67, 33.41, 30.73, 21.52. Chiral HPLC: (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)sulfamide was eluted in MeOH: 98.6% ee, tR=7.63 min (Chiral Method 2).

Workup

  1. customPrepared
  2. customthe solvent was evaporated
  3. customthe residue was purified by column chromatography
  4. customAdditional purification
  5. customby recrystallization from MeOH

Sources & evidence

ORD record
ord-c3b2a974b3ff4215aa746f4798b2139a
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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