Trifluoroacetic acid → HCID 86708497, compound

HRID 1430820Notes

Reaction equation

HRID 1430820 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([NH:15][C:16]2[N:21]=[C:20]([N:22]([CH:32]3[CH2:34][CH2:33]3)CC3C=CC(OC)=CC=3)[C:19]3=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]3[N:17]=2)=[CH:13][C:12]([C:40]#[N:41])=[CH:11][C:10]=1[N:42]1[CH2:47][CH2:46][C@@H:45]([NH:48]C(=O)OC(C)(C)C)[C@H:44]([O:56][Si:57]([CH:64]([CH3:66])[CH3:65])([CH:61]([CH3:63])[CH3:62])[CH:58]([CH3:60])[CH3:59])[CH2:43]1.C1(OC)C=CC=CC=1>ClCCl>[NH2:48][C@@H:45]1[CH2:46][CH2:47][N:42]([C:10]2[C:9]([Cl:8])=[C:14]([NH:15][C:16]3[N:21]=[C:20]([NH:22][CH:32]4[CH2:33][CH2:34]4)[C:19]4=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]4[N:17]=3)[CH:13]=[C:12]([C:40]#[N:41])[CH:11]=2)[CH2:43][C@H:44]1[O:56][Si:57]([CH:61]([CH3:63])[CH3:62])([CH:64]([CH3:66])[CH3:65])[CH:58]([CH3:59])[CH3:60]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 131732382HCID 131732382, compound

Product 1

HCID 86708497HCID 86708497, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
30 °C

Procedure

TFA (1 mL, 3.24 mmol) was added to a solution of tert-butyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-((triisopropylsilyl)oxy)piperidin-4-yl)carbamate (184 mg, 0.219 mmol) and anisole (20 μl, 0.183 mmol) in dichloromethane (1 mL) and the reaction solution was stirred at 30° C. overnight. LCMS showed completion of reaction. The reaction mixture was diluted with dichloromethane and washed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10), the organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 1-4% methanol/dichloromethane). 2-((3-((3R,4R)-4-amino-3-((triisopropylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (126 mg) was obtained as a white solid.

Workup

  1. customcompletion of reaction
  2. washwashed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10)
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (24 g column, eluting with 1-4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-0dd12aa86741482c98dbe9e116ee3971
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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