Water → HCID 11753487, compound

HRID 1678153Notes

Reaction equation

HRID 1678153 reaction equation
[P:1](Cl)([O:6][CH2:7][CH3:8])([O:3][CH2:4][CH3:5])=[O:2].[C:10]([C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]([CH:29]=[O:30])=[C:21]2[N:31]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][OH:39])[CH2:33][CH2:32]2)=[CH:16][CH:15]=1)([CH3:13])([CH3:12])[CH3:11].C(N(CC)CC)C.O>O1CCCC1>[CH2:4]([O:3][P:1](=[O:2])([O:6][CH2:7][CH3:8])[O:39][CH2:38][CH2:37][N:34]1[CH2:35][CH2:36][N:31]([C:21]2[N:20]([C:17]3[CH:18]=[CH:19][C:14]([C:10]([CH3:13])([CH3:11])[CH3:12])=[CH:15][CH:16]=3)[C:28]3[C:23]([C:22]=2[CH:29]=[O:30])=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:32][CH2:33]1)[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 13139Diethyl chlorophosphateHCID 11188937HCID 11188937, compound

Product 1

HCID 11753487HCID 11753487, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl chlorophosphate (0.22 mL, 1.52 mmol) is added to a solution of 1-(4-tert-butylphenyl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-indole -3-carboxaldehyde (510 mg, 1.26 mmol) and triethylamine (0.35 mL, 2.49 mmol) in tetrahydrofuran (5 mL). The resulting orange solution is stirred overnight at room temperature. Water is added and the mixture is extracted with ethyl acetate. The combined ethyl acetate layers are washed with water, with brine, dried and concentrated to give an oil that is purified by chromatography eluting with ethyl acetate and ethyl acetate-5% methanol to afford the phosphoric acid 2-{4-[1-(4-tert-butylphenyl)-3-formyl-1H-indol-2-yl]-piperazin-1-yl}-ethyl ester diethyl ester (280 mg, 68% yield) as a white powder. ESI/MS 542 (M+H) Rt=3.52 min; 1H NMR 10.13 (1H, s); 8.11 (1H, d, J=6 Hz); 7.66 (2H, d, J=6 Hz); 7.46 (2H, d, J=9 Hz); 7.19 (2H, m); 6.92 (1H, d, 9 Hz); 4.04 (6H, m); 3.33 (2H, br s); 3.26 (4H, br s); 2.49 (4H, br s); 1.36 (9H, s); 1.30 (6H, t).

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe combined ethyl acetate layers are washed with water, with brine
  3. customdried
  4. concentrationconcentrated
  5. customto give an oil that
  6. customis purified by chromatography
  7. washeluting with ethyl acetate and ethyl acetate-5% methanol

Sources & evidence

ORD record
ord-3d95cd6e1e7d49e8992595b0c81640b9
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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