Triethylamine → HCID 45121523, compound

HRID 448439Notes

Reaction equation

HRID 448439 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([OH:13])=O)[N:2]=1.S(Cl)(Cl)=O.Cl.[NH2:19][CH2:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:22]=1[C:23](=[O:39])[N:24]([CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38])[C:25]2=[O:30].C(N(CC)CC)C>C1COCC1>[O:38]=[C:32]1[CH:31]([N:24]2[C:23](=[O:39])[C:22]3[C:26](=[CH:27][CH:28]=[CH:29][C:21]=3[CH2:20][NH:19][C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)=[O:13])[C:25]2=[O:30])[CH2:36][CH2:35][C:34](=[O:37])[NH:33]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 124656Isoquinoline-3-carboxylic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 45121523HCID 45121523, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of isoquinoline 3-carboxylic acid (0.39 g, 2.0 mmol) and thionyl chloride (10 mL) was heated to reflux for 1 hour. Excess thionyl chloride was removed under vacuum. To the acid chloride, was then added 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), THF (30 mL) and triethylamine (0.61 g, 6.0 mmol), and the resulting mixture was stirred at reflux for 90 minutes. The solvent was evaporated and the crude residue was chromatographed using a methylene chloride-methanol gradient, eluting 0.67 g of the product with 96:4 methylene chloride-methanol, in 76% yield: mp 198-200° C.; 1H NMR (DMSO-d6) δ 2.07-2.11 (m, 1H), 2.53-2.66 (m, 2H), 2.85-2.97 (m, 1H), 5.02 (d, J=6.3 Hz, 2H), 5.19 (dd, J=12.6 Hz, d=5.3 Hz, 1H), 7.71-7.92 (m, 5H), 8.21 (d, J=7.8 Hz, 1H), 8.28 (d, J=7.8 Hz, 1H) 8.59 (s, 1H), 9.43 (s, 1H), 9.65 (t, J=6.3 Hz, 1H), 11.17 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 31.0, 38.5, 48.9, 120.0, 121.9, 127.2, 127.8, 128.0, 129.2, 129.3, 131.4, 131.6, 133.0, 134.8, 135.4, 139.2, 143.4, 151.7, 164.7, 167.0, 167.6, 169.9, 172.8; Anal. calcd for C24H18N4O5.0.5H2O: C, 63.85; H, 4.24; N, 12.41. Found: C, 63.85; H, 3.93; N, 12.31.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 hour
  3. customExcess thionyl chloride was removed under vacuum
  4. temperatureat reflux for 90 minutes
  5. customThe solvent was evaporated
  6. customthe crude residue was chromatographed
  7. washeluting 0.67 g of the product with 96:4 methylene chloride-methanol

Sources & evidence

ORD record
ord-a8771cafe78144a6ae762ad90da8abf3
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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