Triethylamine → HCID 15953808, compound

HRID 1172369Notes

Reaction equation

HRID 1172369 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][C@@H:12]([NH:17][C:18]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[C:27](=[O:36])[NH:28][C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:22][CH2:21]2)=[O:19])[C:13](OC)=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.[NH2:37][C@H:38]([C:51](=[O:64])[N:52]1[CH2:57][CH2:56][N:55]([C:58]2[CH:63]=[CH:62][N:61]=[CH:60][CH:59]=2)[CH2:54][CH2:53]1)[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][C@@H:12]([NH:17][C:18]([N:20]2[CH2:21][CH2:22][CH:23]([C:26]3[C:27](=[O:36])[NH:28][C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:24][CH2:25]2)=[O:19])[C:13]([NH:37][C@H:38]([C:51](=[O:64])[N:52]2[CH2:57][CH2:56][N:55]([C:58]3[CH:59]=[CH:60][N:61]=[CH:62][CH:63]=3)[CH2:54][CH2:53]2)[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44](=[O:50])[O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11589233HCID 11589233, compoundHCID 58826320HCID 58826320, compound

Product 1

HCID 15953808HCID 15953808, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-methyl 3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamido)propanoate (95 mg, 0.2 mmol) in DMF (2.0 mL) was added (S)-tert-butyl 5-amino-6-oxo-6-(4-(pyridin-4-yl)piperazin-1-yl)hexylcarbamate (78 mg, 0.2 mmol) followed by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (71 mg, 0.22 mmol) and triethylamine (1 mL). After stirring at room temperature for 2 h, the solvent was removed and the crude product was purified by flash chromatography using 7% methanol in dichloromethane containing 2% ammonium hydroxide (ammonia content 28-30%) to give tert-butyl (S)-5-((R)-3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamido)propanamido)-6-oxo-6-(4-(pyridin-4-yl)piperazin-1-yl)hexylcarbamate in 87% yield as white solid. 1H-NMR (CD3OD) δ 8.11-8.10 (m, 2H), 7.97 (s, 1H), 7.61 (d, J=7.5 Hz, 1H), 7.50-7.44 (m, 3H), 7.32-7.30 (d, J=7.5 Hz, 2H), 7.23-7.20 (m, 1H), 7.13 (s, 1H), 6.77 (d, J=6.5 Hz, 1H), 4.83-4.81 (m, 1H), 4.67-4.65 (m, 1H), 4.14-4.08 (m, 2H), 3.82-3.78 (m, 2H), 3.69-3.62 (m, 1H), 3.60-3.53 (m, 1H), 3.48-2.80 (m, 10H), 2.52 (s, 3H), 1.84-1.78 (m, 2H), 1.69-1.61 (m, 1H), 1.40 (s, 9H), 1.49-1.11 (m, 8H); MS (ESI) 847 (M+H) ; Rf=2.34.

Workup

  1. customthe solvent was removed
  2. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-1d8447ca15a8411ab88602c0d091a745
Source dataset
uspto-grants-2010_11
Patent number
US07834007B2

Reaction notes

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