Triethylamine → (S)-4-(5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide

HRID 1892135Notes

Reaction equation

HRID 1892135 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:23]=[CH:24][CH:25]=1)[C:17]([NH:19][CH:20]([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.[Br:33][C:34]1[C:42]2[C:41]([N:43]3[CH2:48][CH2:47][NH:46][C@@H:45]([CH3:49])[CH2:44]3)=[N:40][CH:39]=[N:38][C:37]=2[N:36]([S:50]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)(=[O:52])=[O:51])[CH:35]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CO>[Br:33][C:34]1[C:42]2[C:41]([N:43]3[CH2:48][CH2:47][N:46]([C:5]([NH:13][C:14]4[CH:25]=[CH:24][CH:23]=[C:16]([C:17](=[O:18])[NH:19][CH:20]([CH3:22])[CH3:21])[CH:15]=4)=[O:11])[C@@H:45]([CH3:49])[CH2:44]3)=[N:40][CH:39]=[N:38][C:37]=2[N:36]([S:50]([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)(=[O:51])=[O:52])[CH:35]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 94429TriphosgeneHCID 30190233-amino-N-(isopropyl)benzamideHCID 68959523(S)-5-bromo-4-(3-methylpiperazin-1-yl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 68728768(S)-4-(5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamideYield 220%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of triphosgene (15 mg, 0.05 mmol) in THF (1 ml) at 0° C. under N2 was added dropwise a solution of 3-amino-N-isopropylbenzamide (25 mg, 0.14 mmol) and triethylamine (43 μL, 0.3 mmol) in THF (1 ml). The mixture was stirred for 15 min at 0° C. and another 15 min at room temperature. The piperazine from step C (65 mg, 0.14 mmol) in THF (1 ml) was added, and the resulting mixture was stirred at room temperature overnight, then quenched with MeOH and K2CO3 (97 mg, 0.70 mmol) and filtered. The solution was concentrated under vacuum and purified by Prep-HPLC to give (S)-4-(5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide (70 mg, 0.11 mmol, 77%). MS (ES+) [M+H]+=641.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. filtrationfiltered
  3. concentrationThe solution was concentrated under vacuum
  4. custompurified by Prep-HPLC

Sources & evidence

ORD record
ord-1d995ce1325e4df3a467ceb5c41df623
Source dataset
uspto-grants-2013_08
Patent number
US08507672B2

Reaction notes

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