Isopropyl chloroformate → HCID 59511497, compound

HRID 1157792Notes

Reaction equation

HRID 1157792 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[C:5]2[NH:21][CH:22]=[C:23]([C:24](=[O:44])[C:25]([N:27]3[CH2:32][CH2:31][N:30]([C:33]4[N:37]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=5)[N:36]=[N:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])[C:4]=12.[C:45](Cl)(=[O:50])[O:46][CH:47]([CH3:49])[CH3:48]>C1COCC1.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:16][CH2:17][N:18]([C:45]([O:46][CH:47]([CH3:49])[CH3:48])=[O:50])[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)=[C:5]2[NH:21][CH:22]=[C:23]([C:24](=[O:44])[C:25](=[O:26])[N:27]3[CH2:32][CH2:31][N:30]([C:33]4[N:37]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=5)[N:36]=[N:35][N:34]=4)[CH2:29][CH2:28]3)[C:4]=12

Participants

5

Reactant 2

HCID 7917Isopropyl chloroformateHCID 59511452HCID 59511452, compound

Product 1

HCID 59511497HCID 59511497, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(4-methoxy-7-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (50 mg, 0.084 mmol) in THF (1 mL) and DMF (1 mL) were added TEA (0.023 mL, 0.168 mmol) and isopropyl carbonochloridate (13.42 mg, 0.109 mmol) at room temperature. The reaction was stirred for 3 hours. The reaction mixture was concentrated under reduced pressure. The resulting crude was purified by prep HPLC to give isopropyl 4-(4-(4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)phenyl)piperazine-1-carboxylate (20 mg, 35%) as white solid. LCMS: m/e 680.58 (M+H)+, ret time 2.49 min (method 4). 1H NMR (500 MHz, MeOD) δ ppm 1.30 (d, J=6.10 Hz, 6H) 3.41-3.50 (m, 6H) 3.50-3.58 (m, 2H) 3.65-3.75 (m, 6H) 3.86-3.93 (m, 2H) 4.14 (s, 3H) 4.95-4.99 (m, 1H) 7.28 (d, J=8.85 Hz, 2H) 7.63 (dd, J=7.32, 4.88 Hz, 1H) 7.77 (d, J=8.55 Hz, 2H) 7.89 (d, J=7.93 Hz, 1H) 8.01 (s, 1H) 8.12-8.20 (m, 1H) 8.67 (s, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe resulting crude was purified by prep HPLC

Sources & evidence

ORD record
ord-26dc4df75cf444298380c62874946950
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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