Water → HCID 15546955, compound

HRID 1069109Notes

Reaction equation

HRID 1069109 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)=[O:3].[NH2:15][C:16]1[CH:24]=[C:23]2[C:19]([CH:20]([CH2:41][Cl:42])[CH2:21][N:22]2[C:25](=[O:40])/[CH:26]=[CH:27]/[C:28]2[N:29]([CH3:39])[CH:30]=[C:31]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])[CH:32]=2)=[CH:18][CH:17]=1.O>N1C=CC=CC=1>[C:34]([NH:33][C:31]1[CH:32]=[C:28](/[CH:27]=[CH:26]/[C:25]([N:22]2[C:23]3[C:19](=[CH:18][CH:17]=[C:16]([NH:15][C:2]([O:4][CH2:5][C:6]4[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=4)=[O:3])[CH:24]=3)[CH:20]([CH2:41][Cl:42])[CH2:21]2)=[O:40])[N:29]([CH3:39])[CH:30]=1)(=[O:38])[CH2:35][CH2:36][CH3:37]

Participants

5

Reactant 3

HCID 962WaterHCID 782054-Nitrobenzyl chloroformate2×HCID 5933245HCID 5933245, compound

Product 1

HCID 15546955HCID 15546955, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

4-Nitrobenzyl chloroformate (52 mg, 0.24 mmol) was added to a solution of 8 (48 mg, 0.12 mmol) in dry pyridine (6 mL) and the yellow solution was stirred at 20° C. More 4-nitrobenzyl chloroformate (52 mg, 0.24 mmol) was added after 30 min. After a further 1 h water was added and the mixture stirred for 30 min until the oil that separated had solidified. The solid was filtered off, washed with water, dried, and triturated with hot EtOAc to give 1-[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-(chloromethyl)-6-[(4-nitrobenzyloxy)carbonyl]aminoindoline (8a) (49 mg, 71%) as a yellow solid, mp 207-209.5° C. 1H NMR [(CD3)2SO] δ6 9.91 (s, 1 H, NH), 9.76 (s, 1 H, NH), 8.40 (s, 1 H, H-7), 8.27 (d, J=8.7 Hz, 2 H, ArHo to NO2), 7.70 (d, J=8.7 Hz, 2 H, ArHm to NO2), 7.54 (d, J=15.0 Hz, 1 H. H-β) 7.28 (d, J=8.2 Hz, 1 H, H-4), 7.22 (d, J=1.5 Hz, 1 H, H-5′), 7.16 (d, J=8.2 Hz, 1 H, H-6), 6.71 (d, J=1.4 Hz, 1 H. H-3′), 6.64 (d, J=15.0 Hz, 1 H, H-α), 5.30 (s, 2 H, ArCH2O), 4.48-4.39 (m, 1 H, H-2), 4.12 (dd, J=10.5, 4.1 Hz, 1 H, ArCH2O), 4.48-4.39 (m, 1 H, H-2), 4.12 (dd, J=10.5, 4.1 Hz, 1 H, H-2), 3.98-3.92 (m, 1 H, CHCH2Cl), 3.85-3.76 (m, 2 H, CHCH2Cl), 3.68 (s, 3H, NCH3), 2.20 (t, J=7.3 Hz, 2 H, CH2CH2CH3), 1.58 (sx, J=7.4 Hz, 2 H, CH2CH2CH3), 0.89 (t, J=7.4 Hz, 3 H, CH2CH2CH3).

Workup

  1. stirringthe mixture stirred for 30 min until the oil
  2. customthat separated
  3. filtrationThe solid was filtered off
  4. washwashed with water
  5. customdried
  6. customtriturated with hot EtOAc

Sources & evidence

ORD record
ord-292145888da346e89af1bfaba1fd1be7
Source dataset
uspto-grants-2001_06
Patent number
US06251933B1

Reaction notes

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