Tert-Butylamine → 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246737Notes

Reaction equation

HRID 246737 reaction equation
[NH2:1][C:2]([CH3:49])([CH3:48])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45](O)=[O:46])=[CH:24][N:25]([C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:20]2=[N:19][CH:18]=1.[C:50]([NH2:54])([CH3:53])([CH3:52])[CH3:51].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[NH2:1][C:2]([CH3:49])([CH3:48])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45]([NH:54][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:46])=[CH:24][N:25]([C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:20]2=[N:19][CH:18]=1

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712808552-(5-(4-Amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

Product 1

HCID 712794972-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 83.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(5-(4-Amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (100 mg, 0.15 mmol), tert-butylamine (0.05 mL, 0.45 mmol) and HATU (68.4 mg, 0.18 mmol) in 10 mL of dry THF was stirred for 4 hours at room temperature. The reaction mixture was evaporated to dryness, the residue was suspended in 50 mL of 0.5 N HCl, and product extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, 62%) as dark oil, material used in the next step without further purification. LCMS: (M+H)+=706.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. extractionproduct extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-60a49f5193d442c98c02c982165725b8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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