Trimethylphosphine → HCID 89783455, compound

HRID 1056399Notes

Reaction equation

HRID 1056399 reaction equation
[N:1]([CH2:4][CH2:5][C@@H:6]1[C:10]2[NH:11][C:12]([C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:23]=3[N:22]=[C:21]([NH:24][C:25]([CH3:28])([CH3:27])[CH3:26])[N:20]([CH3:29])[C:19]4=[O:30])=[CH:13][C:9]=2[C:8](=[O:31])[NH:7]1)=[N+]=[N-].CP(C)C>C1COCC1.O>[NH2:1][CH2:4][CH2:5][C@@H:6]1[C:10]2[NH:11][C:12]([C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:23]=3[N:22]=[C:21]([NH:24][C:25]([CH3:28])([CH3:26])[CH3:27])[N:20]([CH3:29])[C:19]4=[O:30])=[CH:13][C:9]=2[C:8](=[O:31])[NH:7]1

Participants

5

Reactant 2

HCID 68983TrimethylphosphineHCID 89793789HCID 89793789, compound

Product 1

HCID 89783455HCID 89783455, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-8-(6-(2-azidoethyl)-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrolo-2-yl)-2-(tert-butylamino)-3-methylquinazolin-4(3H)-one (504a, 200 mg, 0.476 mmol) in THF (7 mL) at RT was added trimethylphosphine (1.0 M in THF, 0.71 mL, 0.71 mmol) followed by 3 drops of water. It was stirred at RT for 30 min then the reaction mixture was concentrated and the crude residue was purified on the ISCO Combiflash RF (24 g Redisep column, using a gradient of 0-20% 2M NH3/MeOH in DCM) affording (R)-8-(6-(2-aminoethyl)-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-2-(tert-butylamino)-3-methylquinazolin-4(3H)-one (504, 65 mg, 0.166 mmol, 35% yield) as a light yellow amorphous solid after drying under vacuum. 1H NMR (400 MHz, MeOH-d4) δ ppm 8.00 (1H, dd, J=8.0, 1.4 Hz), 7.93 (1H, dd, J=7.5, 1.5 Hz), 7.21 (1H, t, J=7.7 Hz), 6.75 (1H, s), 4.73 (1H, dd, J=7.6, 4.1 Hz), 3.56 (3H, s), 2.74-2.93 (2H, m), 2.12-2.26 (1H, m), 1.85-1.98 (1H, m), 1.57-1.67 (9H, s). m/z (ESI, +ve) 395.0 (M+1)+.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe crude residue was purified on the ISCO Combiflash RF (24 g Redisep column

Sources & evidence

ORD record
ord-2171285cddea497caa4b1ecf8b2c73f4
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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