Morpholine → [3-Methyl-4-(piperidin-4-yloxy)-phenyl]-(6-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-amine

HRID 731910Notes

Reaction equation

HRID 731910 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]3[C:23]4[CH:31]=[C:30](F)[N:29]=[CH:28][C:24]=4[N:25]=[CH:26][N:27]=3)=[CH:17][C:16]=2[CH3:33])[CH2:10][CH2:9]1)=O)(C)(C)C.CCN(CC)CC.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>CS(C)=O.CCOC(C)=O>[CH3:33][C:16]1[CH:17]=[C:18]([NH:21][C:22]2[C:23]3[CH:31]=[C:30]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[N:29]=[CH:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH:19]=[CH:20][C:15]=1[O:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 690530484-[4-(6-Fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69057517[3-Methyl-4-(piperidin-4-yloxy)-phenyl]-(6-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-amine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-[4-(6-Fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.21 mmol), NEt3 (0.67 g, 6.63 mmol), and morpholine (0.57 g, 6.63 mmol) in DMSO (10 mL) was heated to 120° C. in a sealed tube. After 24 h the reaction was diluted with EtOAc, the organic layer was washed 2× 1N NaOH and 2× water. The organic layer was treated with HCl (g) and the title compound was collected by filtration as a yellow solid (0.63 g, 67%). LRMS: 421.3 (MH+). 1H NMR (DMSO-d6, 400 MHz): δ 9.15 (br. s, 1H), δ 9.05 (br. s, 1H), δ 8.92 (s, 1H), δ 8.65 (s, 1H), δ 8.18 (s, 1H), δ 7.49-7.51 (m, 2H), δ 7.096 (d, J=9.55, 1H), δ 4.66-4.69 (m, 1H), δ 3.65-3.73 (m, 8H), δ 3.16 (br. s, 2H), δ 3.06 (br. s, 2H), δ 2.17 (s, 3H), δ 2.07-2.13 (m, 2H), δ 1.85-1.94 (m, 2H).

Workup

  1. washthe organic layer was washed 2× 1N NaOH and 2× water
  2. additionThe organic layer was treated with HCl (g)
  3. filtrationthe title compound was collected by filtration as a yellow solid (0.63 g, 67%)

Sources & evidence

ORD record
ord-7ec22dc88d3b42fe9aa929bf2b506179
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

Loading…