Ammonia → HCID 86722064, compound

HRID 525049Notes

Reaction equation

HRID 525049 reaction equation
BrBr.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[Cl:29][C:30]1[CH:34]=[CH:33][N:32]([NH:35][C:36](=O)[CH2:37][N:38]2[CH:46]=[N:45][C:44]3[C:39]2=[N:40][CH:41]=[N:42][C:43]=3[NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C:31]=1[C:56]([NH:58][C@@H:59]([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[CH3:60])=[O:57].N>ClCCl>[Cl:29][C:30]1[CH:34]=[CH:33][N:32]2[C:31]=1[C:56](=[O:57])[N:58]([C@@H:59]([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[CH3:60])[C:36]([CH2:37][N:38]1[CH:46]=[N:45][C:44]3[C:39]1=[N:40][CH:41]=[N:42][C:43]=3[NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[N:35]2

Participants

7

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 24408BromineHCID 86722065HCID 86722065, compound

Product 1

HCID 86722064HCID 86722064, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of bromine (37 mg, 0.24 mmol) in dichloromethane (100 μL) was added dropwise to a solution of triphenylphosphine (63 mg, 0.24 mmol) in dichloromethane (1 ml) under nitrogen. The solution was stirred for 30 min, and triethylamine (78 μL, 0.56 mmol) and tert-butyl [9-(2-{[3-chloro-2-({[(1R)-1-phenylethyl]amino}carbonyl)-1H-pyrrol-1-yl]amino}-2-oxoethyl)-9H-purin-6-yl]carbamate (100 mg, 0.19 mmol) were added. The reaction mixture was refluxed for 1.5 h, and quenched with 10% aqueous sodium bicarbonate solution. The organic phase was separated, dried (sodium sulphate) and concentrated to obtain an oil that was treated with 6 ml of a 7M methanolic solution of ammonia at 60° C. in a sealed vessel. The solvent was then evaporated to obtain 66 mg (34% yield, 48% purity) of tert-butyl [9-({5-chloro-4-oxo-3-[(1R)-1-phenylethyl]-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl}methyl)-9H-purin-6-yl]carbamate.

Workup

  1. temperatureThe reaction mixture was refluxed for 1.5 h
  2. customquenched with 10% aqueous sodium bicarbonate solution
  3. customThe organic phase was separated
  4. dry with materialdried (sodium sulphate)
  5. concentrationconcentrated
  6. customto obtain an oil that
  7. customThe solvent was then evaporated

Sources & evidence

ORD record
ord-25cc1485662b4825b437b8736ac11937
Source dataset
uspto-grants-2016_05
Patent number
US09340547B2

Reaction notes

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