Dimethylacetamide → Diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate

HRID 511810

Reaction equation

HRID 511810 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:13]([O:15][P:16]([CH2:21][C:22]([OH:24])=O)([O:18][CH2:19][CH3:20])=[O:17])[CH3:14].[Br:25][C:26]1[CH:27]=[C:28]([NH:33][C:34]2[C:35]3[CH:43]=[C:42]([NH2:44])[N:41]=[CH:40][C:36]=3[N:37]=[CH:38][N:39]=2)[CH:29]=[CH:30][C:31]=1[Br:32].CC(N(C)C)=O>C1COCC1.O.ClCCl.CO>[Br:25][C:26]1[CH:27]=[C:28]([NH:33][C:34]2[C:35]3[CH:43]=[C:42]([NH:44][C:22](=[O:24])[CH2:21][P:16](=[O:17])([O:15][CH2:13][CH3:14])[O:18][CH2:19][CH3:20])[N:41]=[CH:40][C:36]=3[N:37]=[CH:38][N:39]=2)[CH:29]=[CH:30][C:31]=1[Br:32]

Participants

8

Reactant 4

HCID 31374DimethylacetamideHCID 36704(Diethoxyphosphinyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 86668941N4-(3,4-dibromophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine

Product 1

HCID 86668942Diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonateYield 95.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred mixture of CDI (2.74 g, 16.9 mmol) and dry THF (13 mL), at room temperature and under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (2.96 g, 15.1 mmol) in THF (10 mL). After addition the reaction mixture was stirred further at 40° C. (bath) for 15 min (whence evolution of gases ceased). A solution of compound 225 (2.38 g, 6.02 mmol) in a mixed solvents of dry THF (7 mL) and DMA (8 mL) was added and stirred further at 40° C. The reaction was monitored by TLC (dichloromethane-MeOH=15:1). After stirred for 4 h, the reaction mixture was poured into water (250 mL) and stirred with petroleum ether (350 mL) at room temperature for 20 min. Petroleum ether layer was decanted. It was repeated once more with petroleum ether (200 mL). The solid was collected by suction filtration; washed with water (5×30 mL) and dried to give diethyl 2-(4-(3,4-dibromophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (234) (3.28 g, 95%); mp 120-124° C.; 1H NMR δ [(CD3)2SO]: 10.89 (s, 1H), 10.41 (s, 1H), 9.04 (s, 1H), 8.88 (s, 1H), 8.67 (s, 1 H), 8.34 (d, J=2.5 Hz, 1H), 7.87 (dd, J=8.8, 2.5 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 4.17-4.03 (m, 4H), 3.32 (d, J=21.6 Hz, 2H), 1.26 (t, J=7.0 Hz, 6H). Anal. Calcd for C19H20Br2N5O4P: C, 39.81; H, 3.52; N, 12.22%. Found C, 39.48; H, 3.78; N, 11.79%.

Workup

  1. additionAfter addition the reaction mixture
  2. stirringstirred further at 40° C
  3. stirringAfter stirred for 4 h
  4. customPetroleum ether layer was decanted
  5. filtrationThe solid was collected by suction filtration
  6. washwashed with water (5×30 mL)
  7. customdried

Sources & evidence

ORD record
ord-4ee94104aa4542c889c2f277aa800e20
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Linked notes

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