2-(Methylamino)ethanol → Ammonia methanol

HRID 1162198Notes

Reaction equation

HRID 1162198 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[O:28][C@H:29]([CH3:34])[C:30](OC)=[O:31])[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1.[CH3:35][NH:36][CH2:37][CH2:38][OH:39]>>[OH:39][CH2:38][CH2:37][N:36]([CH3:35])[C:30](=[O:31])[C@H:29]([O:28][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:27]=1[C:18]([NH:17][C:13]1[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=1)[N:8]([CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)[N:9]=[CH:10]3)=[N:19][CH:20]=[N:21]2)[CH3:34].[NH3:1].[CH3:26][OH:28]

Participants

4

Reactant 2

HCID 80162-(Methylamino)ethanolHCID 86627834methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

Product 2

HCID 16116960(2R)-N-(2-Hydroxyethyl)-N-methyl-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanamideHCID 21705897Ammonia methanolYield 5%

Conditions

Temperature
100 °C

Procedure

A stirred suspension of methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate (200 mg, 0.44 mmol) in 2-(methylamino)-ethanol (2 ml) was heated in a microwave reactor at 100° C. for 30 minutes. The 2-(methylamino)-ethanol was evaporated under high vacuum and the residue was partitioned between water and DCM. The organic phase was washed with brine, dried and evaporated to a gum. The title compound was isolated by chromatography (silica, 5% 2M NH3-methanol in DCM) as a white solid after trituration with ether (126 mg, 58%); NMR spectrum (393 K) 1.65 (d, 3H), 3.07 (s, 2H), 3.39-3.66 (m, 5H), 4.40 (s, 1H), 5.71 (s, 2H), 5.76-5.83 (m, 1H), 7.05 (d, 1H), 7.20 (d, 1H), 7.23-7.28 (m, 1H), 7.35 (d, 1H), 7.58 (d, 1H), 7.65-7.73 (m, 2H), 7.84 (dd, 1H), 8.07 (s, 1H), 8.45 (s, 1H), 8.48 (s, 1H), 8.52 (d, 1H), 10.86 (s, 1H); Mass spectrum MH+ 498.

Workup

  1. customThe 2-(methylamino)-ethanol was evaporated under high vacuum
  2. customthe residue was partitioned between water and DCM
  3. washThe organic phase was washed with brine
  4. customdried
  5. customevaporated to a gum

Sources & evidence

ORD record
ord-33961ca0660946bd900af2abab79050d
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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