2-(Ethylamino)ethanol → Defosbarasertib

HRID 1864480Notes

Reaction equation

HRID 1864480 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:21]=[C:20]([CH2:22][C:23]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=4)=[O:24])[NH:19][N:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][CH:7]=1.[CH2:33]([NH:35][CH2:36][CH2:37][OH:38])[CH3:34].CN(C)C(=O)C>O>[CH2:33]([N:35]([CH2:36][CH2:37][OH:38])[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:21]=[C:20]([CH2:22][C:23]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=4)=[O:24])[NH:19][N:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][CH:7]=1)[CH3:34]

Participants

5

Reactant 3

HCID 80722-(Ethylamino)ethanolHCID 31374DimethylacetamideHCID 162214542-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide

Product 1

HCID 16007391DefosbarasertibYield 90%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

2-(3-{[7-(3-Chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide and 2-(ethylamino)ethanol (12 molar equivalents) were added to N,N-dimethylacetamide under an inert atmosphere (such as provided by nitrogen) and the mixture heated to 90° C. with stirring. After 12 hours, water was added in a controlled manner and the batch seeded with product whilst hot. The mixture was cooled to 20° C. in a carefully controlled manner to crystallise the product in the required form. The product was then filtered and washed with a mixture of water/N,N-dimethylacetamide and acetonitrile. Following this, the cake was slurried for a period with warm acetonitrile (40° C.), filtered, washed with more acetonitrile and then dried (in vacuo or under a stream of nitrogen) to afford the anhydrous 2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide as an off-white solid in a yield of ˜90%.

Workup

  1. temperatureThe mixture was cooled to 20° C. in a carefully controlled manner
  2. customto crystallise the product in the required form
  3. filtrationThe product was then filtered
  4. washwashed with a mixture of water/N,N-dimethylacetamide and acetonitrile
  5. waitwas slurried for a period with warm acetonitrile (40° C.)
  6. filtrationfiltered
  7. washwashed with more acetonitrile
  8. customdried (in vacuo

Sources & evidence

ORD record
ord-c5eeabea290d42c69215d824814e6b69
Source dataset
uspto-grants-2009_12
Patent number
US07625910B2

Reaction notes

Loading…