Phosphorus oxychloride → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamate

HRID 341012Notes

Reaction equation

HRID 341012 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[Cl:39])=[O:29])[CH2:16][C:17](=O)[NH:18][CH2:19][C:20]2[CH:25]=[N:24][CH:23]=[CH:22][N:21]=2)[N:2]=1.P(Cl)(Cl)(Cl)=O>C(Cl)Cl>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[Cl:39])=[O:29])[CH2:16][C:17]2[N:21]3[CH:22]=[CH:23][N:24]=[CH:25][C:20]3=[CH:19][N:18]=2)[N:2]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 57947597(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate

Product 1

HCID 57947628(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamateYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate (650 mg, 1.12 mmol) and DCM (50 mL) were added phosphoryl chloride (0.514 mL, 0.00561 mol). The resulting mixture was stirred at RT for overnight. The resulting solution was concentrated. The resulting residue was purified on prep-HPLC (ACN/H2O with 0.1% HCOOH) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamate (0.27 g, 43%). LRMS (M+H+) m/z 562.1

Workup

  1. concentrationThe resulting solution was concentrated
  2. customThe resulting residue was purified on prep-HPLC (ACN/H2O with 0.1% HCOOH)

Sources & evidence

ORD record
ord-f7326d495bbb4b8e8ce4e5d531f1f011
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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