Diisopropylethylamine → 2-(5-(3-(4-isopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-ylamino)-acetonitrile

HRID 634208Notes

Reaction equation

HRID 634208 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]4[O:23][C:22](=O)[NH:21][N:20]=4)[CH:17]=3)[NH:12][CH:11]=2)[N:5]=1)([CH3:3])[CH3:2].Cl.[NH2:26][CH2:27][C:28]#[N:29].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O>[CH:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]4[O:23][C:22]([NH:29][CH2:28][C:27]#[N:26])=[N:21][N:20]=4)[CH:17]=3)[NH:12][CH:11]=2)[N:5]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11491918Aminoacetonitrile hydrochlorideHCID 683284605-(3-(4-isopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2(3H)-one

Product 1

HCID 665547312-(5-(3-(4-isopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-ylamino)-acetonitrileYield 11.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(3-(4-isopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2(3H)-one (350 mg, in about 60% pure) in DMF (4 mL) at RT was sequentially added 2-aminoacetonitrile hydrochloride (302 mg, 3.27 mmol) (Alfa Aesar), diisopropylethylamine (0.79 mL, 4.57 mmol) and BOP (530 mg, 1.20 mmol) (Aldrich). After the reaction was stirred at RT for 18 h, it was diluted with H2O (10 mL) and extracted with EtOAc (3×25 mL). The aqueous layer was discarded. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified on a silica gel column eluting with 25-100% EtOAc in Hex to give 2-(5-(3-(4-isopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-ylamino)-acetonitrile (45 mg) as a brown amorphous solid. MS (ESI, pos. ion) m/z: 360.0 (M+1). 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.99 (1H, br.), 9.16 (1H, s), 8.69 (1H, d, J=5.1 Hz), 8.49 (1H, t, J=5.7 Hz), 8.33 (1H, m), 7.73 (1H, d, J=8.2 Hz), 7.62 (1H, d, J=8.6 Hz), 7.16 (1H, d, J=5.1 Hz), 4.43 (2H, d, J=5.7 Hz), 3.06 (1H, dt, J=13.7, 6.8 Hz), 1.37 (6H, d, J=6.8 Hz).

Workup

  1. customat RT
  2. extractionextracted with EtOAc (3×25 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified on a silica gel column
  8. washeluting with 25-100% EtOAc in Hex

Sources & evidence

ORD record
ord-d2a016a753594dd799d6232d65740afc
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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