Diisopropylethylamine → HCID 89927751, compound

HRID 1408186Notes

Reaction equation

HRID 1408186 reaction equation
[CH2:1]([N:3]([CH2:59][CH3:60])[C:4]1[CH:5]=[CH:6][C:7]([NH:30][C:31](=[O:58])[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][O:51][CH2:52][CH2:53][O:54][CH2:55][CH2:56][OH:57])[CH:33]=2)=[C:8]([C:10]2[CH:11]=[C:12]([CH:27]=[CH:28][N:29]=2)[C:13]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[O:14])[CH:9]=1)[CH3:2].C(N(C(C)C)CC)(C)C.C1C([N+]([O-])=O)=CC=C([Cl-][C:80]([O-])=[O:81])C=1.[O:83]1[CH2:88][CH2:87][N:86]([CH2:89][CH2:90][NH2:91])[CH2:85][CH2:84]1>C(Cl)Cl>[O:83]1[CH2:88][CH2:87][N:86]([CH2:89][CH2:90][NH:91][C:80](=[O:81])[O:57][CH2:56][CH2:55][O:54][CH2:53][CH2:52][O:51][CH2:50][CH2:49][O:48][CH2:47][CH2:46][O:45][CH2:44][CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38][C:34]2[CH:35]=[CH:36][CH:37]=[C:32]([C:31](=[O:58])[NH:30][C:7]3[CH:6]=[CH:5][C:4]([N:3]([CH2:1][CH3:2])[CH2:59][CH3:60])=[CH:9][C:8]=3[C:10]3[CH:11]=[C:12]([C:13](=[O:14])[NH:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=4)[CH:27]=[CH:28][N:29]=3)[CH:33]=2)[CH2:85][CH2:84]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4082852-MorpholinoethylamineHCID 89936939HCID 89936939, compound

Product 1

HCID 89927751HCID 89927751, compoundYield 33.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of Example 168 (50 mg, 0.060 mmol) and diisopropylethylamine (31 μL, 0.18 mmol) in DCM (1 mL) was added 4-nitrophenylchloroformate (52 mg, 0.26 mmol) and the solution stirred for 1 h. 2-Morpholinoethanamine (46 μL, 0.36 mmol) was then added and the solution stirred for 1 h, then the solvent removed and the residue purified by reverse-phase HPLC eluting with a water/acetonitrile gradient containing 0.1% TFA and lyophilized to give 20 mg (25%) of the product as the tri-TFA salt. MS (ES, m/z) 997 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 9.54 (t, J=6.0 Hz, 1H), 9.25 (d, J=2.6 Hz, 1H), 9.17 (d, J=9.1 Hz, 1H), 8.92-8.83 (m, 2H), 8.08 (s, 1H), 8.03 (dd, J=5.1, 1.4 Hz, 1H), 7.98 (dt, J=7.0, 1.9 Hz, 1H), 7.69 (s, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.58-7.46 (m, 3H), 7.46-7.35 (m, 2H), 6.27 (s, 1H), 4.74 (d, J=6.0 Hz, 2H), 4.68 (s, 2H), 4.23-4.12 (m, 2H), 4.02-3.82 (m, 4H), 3.74-3.50 (m, 22H), 3.25 (t, J=5.6 Hz, 2H), 2.93 (t, J=12.0 Hz, 2H), 1.27 (t, J=7.2 Hz, 6H).

Workup

  1. stirringthe solution stirred for 1 h
  2. customthe solvent removed
  3. customthe residue purified by reverse-phase HPLC
  4. washeluting with a water/acetonitrile gradient
  5. additioncontaining 0.1% TFA

Sources & evidence

ORD record
ord-a5244f8386f2440da163f5545ffbd80a
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

Loading…