HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Water → {1-[4-(7-Amino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872332
Notes
Print preview

Reaction equation

HRID 872332 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[C:25](C(O)=O)[CH:24]=[CH:23][N:22]4[C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.C([N:40](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>[Pd].CO.CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[C:25]([NH2:40])[CH:24]=[CH:23][N:22]4[C:30]=3[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH2:12]1)([CH3:3])([CH3:2])[CH3:4]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azide2×HCID 666649662-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridine-7-carboxylic acid

Product 1

HCID 66665799{1-[4-(7-Amino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester
Yield 129.9%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-[4-(1-tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridine-7-carboxylic acid (1.20 g, 0.86 mmol) and 10% palladium on carbon (0.2 g) in MeOH (20 mL) in DMF (40 mL) and water (3.4 mL) was added triethylamine (0.38 mL, 2.73 mmol, 1.1 equiv) followed by diphenylphosphoryl azide (751 mg, 2.73 mmol, 1.1 equiv). The resulting mixture was stirred at room temperature 10 minutes, at 100° C. for 6 h, at room temperature for 12 h. To the resulting mixture was added triethylamine (0.38 mL, 2.73 mmol, 1.1 equiv) followed by diphenylphosphoryl azide (751 mg, 2.73 mmol, 1.1 equiv). The resulting mixture was heated at 100° C. for 12 h. The resulting mixture was separated between EtOAc (100 mL) and water (50 mL). The organic phase was dried (Na2SO4 anh) and concentrated under reduced pressure. The remaining material (1.4 g) was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 100% CH2Cl2 for 3.5 min., gradient to 90% CH2Cl2: 10% MeOH over 1 min.; 90% CH2Cl2: 10% MeOH for 5.5 min., gradient to 80% CH2Cl2: 20% MeOH over 6 min., 80% CH2Cl2: 20% MeOH for 10.2 min.) to give {1-[4-(7-amino-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (508 mg, 45%):

Workup

  1. temperatureThe resulting mixture was heated at 100° C. for 12 h
  2. customThe resulting mixture was separated between EtOAc (100 mL) and water (50 mL)
  3. dry with materialThe organic phase was dried (Na2SO4 anh)
  4. concentrationconcentrated under reduced pressure
  5. customThe remaining material (1.4 g) was purified
  6. wait100% CH2Cl2 for 3.5 min.
  7. waitgradient to 90% CH2Cl2: 10% MeOH over 1 min.
  8. wait90% CH2Cl2: 10% MeOH for 5.5 min.
  9. waitgradient to 80% CH2Cl2: 20% MeOH over 6 min.

Sources & evidence

ORD record
ord-1e2173c622eb48d0a6fb21cdc5044da7
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08975265B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes