L-(+)-Cysteine → S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine

HRID 715843Notes

Reaction equation

HRID 715843 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([C:14]3[S:15][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH2:24][C:25]5([CH3:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]5)[CH:23]=4)=[CH:17][CH:18]=3)=[O:13])=[CH:6][C:5]=12.CN1CCOCC1.Br[CH2:40][C:41]([NH:43][CH2:44][CH2:45][C:46]([O:48]N1C(=O)CCC1=O)=O)=[O:42].[NH2:56][C@@H:57]([CH2:61][SH:62])[C:58]([OH:60])=[O:59]>C(N(CC)C(C)C)(C)C.O.C(O)(C(F)(F)F)=O>[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([C:14]3[S:15][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH2:24][C:25]5([CH3:31])[CH2:30][CH2:29][N:28]([C:46](=[O:48])[CH2:45][CH2:44][NH:43][C:41](=[O:42])[CH2:40][S:62][CH2:61][C@@H:57]([C:58]([OH:60])=[O:59])[NH2:56])[CH2:27][CH2:26]5)[CH:23]=4)=[CH:17][CH:18]=3)=[O:13])=[CH:6][C:5]=12

Participants

8

Reactant 4

HCID 5862L-(+)-CysteineHCID 79724-MethylmorpholineHCID 4463814Succinimidyl 3-(bromoacetamido)propionateHCID 86702099N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

Product 1

HCID 86702102S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine

Reagents, catalysts & solvents 3

HCID 6422Trifluoroacetic acidCatalystHCID 962WaterSolventHCID 81531DiisopropylethylamineSolvent2×

Procedure

A suspension of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.050 g, 0.099 mmol) and 4-methylmorpholine (0.054 ml, 0.493 mmol) in N,N-diisopropylethylamine (0.5 ml) was added to 2,5-dioxopyrrolidin-1-yl 3-(2-bromoacetamido)propanoate (0.036 g, 0.118 mmol) in N,N-diisopropylethylamine (0.5 ml) and the mixture was stirred at room temperature. After 1 hour, (R)-2-amino-3-mercaptopropanoic acid (0.060 g, 0.493 mmol) as a solution in water (1 ml) was added. After 1 hour, a few drops of TFA were added to form a homogeneous solution and the mixture was purified by chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.28 (t, J=5.9 Hz, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.47 (s, 2H), 8.30 (d, J=1.9 Hz, 1H), 8.21 (t, J=5.6 Hz, 1H), 8.17-8.09 (m, 2H), 7.84 (s, 1H), 7.81-7.74 (m, 2H), 7.44 (dd, J=7.0, 1.1 Hz, 1H), 7.27 (d, J=3.8 Hz, 1H), 4.65 (d, J=5.8 Hz, 2H), 4.20 (dd, J=7.5, 4.3 Hz, 1H), 4.06 (s, 2H), 3.90-3.78 (m, 2H), 3.35-2.94 (m, 8H), 2.59-2.41 (m, 2H), 1.57-1.19 (m, 4H), 0.95 (s, 3H); MS (ESI(+)) m/e 667 (M+H)+.

Workup

  1. waitAfter 1 hour
  2. customto form a homogeneous solution
  3. customthe mixture was purified by chromatography

Sources & evidence

ORD record
ord-87cd9f909688403bb95867ef16258432
Source dataset
uspto-grants-2015_11
Patent number
US09187472B2

Reaction notes

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