Triethylamine → HCID 178476966, compound

HRID 1525205Notes

Reaction equation

HRID 1525205 reaction equation
[OH:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:3]=1.CCN(CC)CC.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:36][CH:37]([C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)[C:38]1[CH:43]=[CH:42][C:41]([P:44](=[O:51])([O:48][CH2:49][CH3:50])[O:45][CH2:46][CH3:47])=[CH:40][CH:39]=1>CN1C(=O)CCC1.O.C(OCC)(=O)C>[OH:1][C:2]1[C:7]([C:8]([NH:36][CH:37]([C:52]2[CH:53]=[CH:54][C:55]([O:58][CH3:59])=[CH:56][CH:57]=2)[C:38]2[CH:39]=[CH:40][C:41]([P:44](=[O:51])([O:48][CH2:49][CH3:50])[O:45][CH2:46][CH3:47])=[CH:42][CH:43]=2)=[O:10])=[CH:6][N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 89463039Diethyl 4-(amino(4-methoxyphenyl)methyl)phenylphosphonateHCID 178524750HCID 178524750, compound

Product 1

HCID 178476966HCID 178476966, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxylic acid, 1-1-h, (580 mg, 2.6 mmol) in NMP (2 ml) was added Et3N (540 mg, 5.2 mmol). The mixture was aged for 15 min at room temperature. To the mixture was added CDI (480 mg, 2.86 mmol) and the resulting mixture was heated to 70° C. for 1 h. To the hot homogeneous solution was then added in one portion diethyl 4-(amino(4-methoxyphenyl)methyl)phenylphosphonate, 1-1-d, (940 mg, 2.6 mmol). Heating was continued for 30 min at 70° C. The reaction mixture was then cooled to room temperature and diluted with water (12 ml) and ethyl acetate (5 ml). The resulting aqueous layer was slowly neutralized to pH=7. The neutralized aqueous layer was then extracted with ethyl acetate. The organic layer was concentrated under vacuum and the residue was purified on silica gel column with the eluent of dichloromethane/methanol=50/1 and subsequently prep-HPLC to provide the product as a white solid, 1-1-1, (260 mg, 18%). 1H NMR (CD3OD, 300 MHz,): δ 8.60 (m, 2H), 8.40 (m, 1H), 7.90 (m, 1H), 7.60 (m, 2H), 7.50 (m, 1H), 7.40 (m, 2H), 7.20 (m, 2H), 6.84 (m, 2H), 6.24 (s, 1H), 3.99 (m, 4H), 3.68 (s, 3H), 1.08 (t, 6H, J=6 Hz).

Workup

  1. temperatureHeating
  2. waitwas continued for 30 min at 70° C
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. extractionThe neutralized aqueous layer was then extracted with ethyl acetate
  5. concentrationThe organic layer was concentrated under vacuum
  6. customthe residue was purified on silica gel column with the eluent of dichloromethane/methanol=50/1

Sources & evidence

ORD record
ord-6bc1deda0dca4e6cb28bb0d2f161e8df
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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