Diisopropylethylamine → HCID 22390486, compound

HRID 1072094Notes

Reaction equation

HRID 1072094 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:21]4=[C:22]([CH2:25]OC(=O)C)[CH:23]=[CH:24][N:20]4[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1.C(OC(=O)[NH:39][C:40]([CH3:44])([CH3:43])[CH2:41][OH:42])(C)(C)C.CCN(C(C)C)C(C)C>C(#N)C>[NH2:39][C:40]([CH3:43])([CH3:44])[CH2:41][O:42][CH2:25][C:22]1[CH:23]=[CH:24][N:20]2[C:21]=1[C:16]([NH:15][C:11]1[CH:10]=[C:9]3[C:14](=[CH:13][CH:12]=1)[N:6]([CH2:5][C:4]1[CH:30]=[CH:31][CH:32]=[C:2]([F:1])[CH:3]=1)[N:7]=[CH:8]3)=[N:17][CH:18]=[N:19]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 14578673tert-butyl N-(1-hydroxy-2-methylpropan-2-yl)carbamateHCID 20802914HCID 20802914, compound

Product 1

HCID 22390486HCID 22390486, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of acetic acid 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethylester (100 mg, 0.24 mmol), (2-hydroxy-1,1-dimethyl-ethyl)-carbamic acid tert-butyl ester 156 mg, 3 equiv) and DIPEA (62 μL, 1.5 equiv) in dry acetonitrile (0.2 mL) in a vial was placed in a microwave reactor (Personal Chemistry's Smith Creator) and irradiated for 10 min at 109° C. The solvent was removed and the residue was taken up in dry DCM (3 mL) and cooled to 0° C. TFA (3 mL) was added and after 1.5 hr, the solvents were removed. The residue was partitioned between DCM and saturated NaHCO3 solution. The organic phase was dried (Na2SO4) and the solvent was removed. Purification by radial chromatography (1 mm silica gel plate, gradient elution with 0 to 5% MeOH in DCM) gave the title compound (13 mg, 12% yield): MS: 460 (M+H)+; HPLC Ret Time: 1.34 min, YMC Xterra ODS S7 3.0×50 mm, 2 min gradient, 5 mL/min).

Workup

  1. customwas placed in a microwave reactor
  2. custom(Personal Chemistry's Smith Creator) and irradiated for 10 min at 109° C
  3. customThe solvent was removed
  4. additionTFA (3 mL) was added and after 1.5 hr
  5. customthe solvents were removed
  6. customThe residue was partitioned between DCM and saturated NaHCO3 solution
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. customthe solvent was removed
  9. customPurification
  10. washby radial chromatography (1 mm silica gel plate, gradient elution with 0 to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-271940b8554e447d854b387debf40c59
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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