1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-[3-(chloromethyl)-6-nitro-indoline-1-carbonyl]-N-[2-(2-pyridyl)ethyl]-1H-indole-6-carboxamide

HRID 1603043Notes

Reaction equation

HRID 1603043 reaction equation
C(O[C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=2)[CH:10]([CH2:20][Cl:21])[CH2:9]1)=[O:7])(C)(C)C.Cl.CN(C)CCCN=C=NCC.C([C:37]1[NH:38][C:39]2[C:44]([CH:45]=1)=[CH:43][CH:42]=[C:41]([C:46]([NH:48][CH2:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][N:52]=1)=[O:47])[CH:40]=2)(O)=O>Cl.CN(C=O)C>[Cl:21][CH2:20][CH:10]1[C:11]2[C:16](=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[N:8]([C:6]([C:37]2[NH:38][C:39]3[C:44]([CH:45]=2)=[CH:43][CH:42]=[C:41]([C:46]([NH:48][CH2:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][N:52]=2)=[O:47])[CH:40]=3)=[O:7])[CH2:9]1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 108289531-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindolineHCID 19608773HCID 19608773, compound

Product 1

HCID 3899062-[3-(chloromethyl)-6-nitro-indoline-1-carbonyl]-N-[2-(2-pyridyl)ethyl]-1H-indole-6-carboxamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

1-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindoline (248 mg, 0.79 mmol) was stirred in HCl-saturated dioxane (8 mL) at 20° C. for 40 min (until tlc indicated complete reaction) and the mixture evaporated. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.30 g, 1.58 mmol) and 2-carboxy-N-[2-(2-pyridinyl)ethyl]indole-6-carboxamide (245 mg, 0.79 mmol) in DMF (20 mL) were added and the orange solution stirred at 20° C. After 24 h the DMF was evaporated, and the residue triturated with EtOAc and aqueous NaHCO3. The solid was filtered off and recrystallised from MeOH to give 2-[[3-(chloromethyl)-6-nitroindolin-1-yl]carbonyl]-N-[2-(2-pyridinyl)ethyl]indole-6-carboxamide as a yellow solid (267 mg, 67%), mp 204-207° C. 1H NMR [(CD3)2SO] δ12.15 (s, 1H, indole NH), 8.99 (d, J=2.1 Hz, 1H, H-7), 8.61 (t, J=5.5 Hz, 1H, amide NH), 8.55-8.52 (m, 1H, H-6"), 8.04 (dd, J=8.3, 2.3 Hz, 1H, H-5), 8.02 (s, 1H, H-3' or H-7'), 7.75 (d, J=8.6 Hz, 1H, H-4 or H-4'), 7.74 (d, J=8.3 Hz, 1H, H-4 or H-4'), 7.71 (dd, J=7.6, 1.9 Hz, 1H, H-4"), 7.56 (dd, J=8.5, 1.3 Hz, 1H, H-5'), 7.31 (d, J=7.7 Hz, 1H, H-3"), 7.28 (d, J=1.4 Hz, 1H, H-3' or H-7'), 7.23 (ddd, J=7.2, 4.9, 0.8 Hz, 1H, H-5"), 4.86 (t, J=10.1 Hz, 1H, H-2), 4.51 (dd, J=10.7, 5.1 Hz, 1H, H-2), 4.19-4.06 (m, 3H, H-3 and CH2Cl), 3.66 (q, J=6.7 Hz, 2H, NHCH2CH2 py), 3.04 (t, J=7.4 Hz, 2H, NHCH2CH2 py); 13C NMR δ166.7 (CONH), 160.4 (CON), 159.2 (C-2"), 147.6, 144.6, 139.9, 135.7, 131.8, 130.8, 128.9 (C-6,8,9,2',6',8',9'), 149.0, 136.4, 123.1, 121.4 (C-3",4",5",6"), 125.5, 121.6, 119.4, 118.8, 112.0, 111.2, 106.1 (C-4,5,7,3',4',5',7'), 54.0 (C-2), 47.0 (CH2Cl), 42.0 (C-3), 39.3, 37.3 (NHCH2CH2 py). A sample was converted to the hydrochloride salt and triturated with hot EtOH to give 2-[[3-(chloromethyl)-6-nitroindolin-1-yl) carbonyl]-N-[2-(2-pyridinyl)ethyl]indole-6-carboxamide hydrochloride as a pale yellow powder, mp 250-255° C. (dec.). Anal. (C26H22ClN5O4.0.25HCl) C,H,N.

Workup

  1. custom(until tlc indicated complete reaction)
  2. customthe mixture evaporated
  3. customAfter 24 h the DMF was evaporated
  4. customthe residue triturated with EtOAc and aqueous NaHCO3
  5. filtrationThe solid was filtered off
  6. customrecrystallised from MeOH

Sources & evidence

ORD record
ord-843ead72c8b642f0bc3f4ff9dc4716c2
Source dataset
uspto-grants-1999_11
Patent number
US05985909

Reaction notes

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