(Diethoxyphosphinyl)acetic acid → HCID 131736636, compound

HRID 1481314Notes

Reaction equation

HRID 1481314 reaction equation
[NH2:1][C@@H:2]1[C:18]2=[N:19][C:15](=[C:16]([Br:28])[N:17]2[CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]2[C:9](=[CH:10][C:11]([NH:29][C:30](=[O:33])[O:31][CH3:32])=[CH:12][CH:13]=2)[NH:8][C:7](=[O:34])[C@H:6]([CH3:35])[CH2:5][CH2:4][CH2:3]1.[Cl:36][C:37]1[C:38]([F:71])=[C:39]([C:44]2[CH2:45][CH2:46]N(C3C4C=C(C=CN=4)C4C=NNC=4NC(=O)C(C)CCC3)C(=O)C=2)[C:40]([F:43])=[CH:41][CH:42]=1.[CH2:72]([O:74][P:75]([CH2:80][C:81](O)=[O:82])([O:77][CH2:78][CH3:79])=[O:76])[CH3:73].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)[O:88]1)CC>C(Cl)Cl>[Br:28][C:16]1[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:27])[CH3:25])[C:18]2[C@@H:2]([N:1]([CH2:46][CH2:45][C:44]([C:39]3[C:40]([F:43])=[CH:41][CH:42]=[C:37]([Cl:36])[C:38]=3[F:71])=[O:88])[C:81](=[O:82])[CH2:80][P:75]([O:77][CH2:78][CH3:79])([O:74][CH2:72][CH3:73])=[O:76])[CH2:3][CH2:4][CH2:5][C@@H:6]([CH3:35])[C:7](=[O:34])[NH:8][C:9]3[C:14]([C:15]=1[N:19]=2)=[CH:13][CH:12]=[C:11]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:10]=3

Participants

6

Reactant 4

HCID 36704(Diethoxyphosphinyl)acetic acidHCID 111923Propylphosphonic anhydrideHCID 131736637HCID 131736637, compoundHCID 136970220HCID 136970220, compound

Product 1

HCID 131736636HCID 131736636, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask was 227A (1.18 g, 1.49 mmol), DCM (47.9 mL) and TEA (1.45 mL, 10.40 mmol). The reaction was stirred for 30 minutes before adding Intermediate 1 (0.301 g, 1.49 mmol). After 4 hours, 2-(diethoxyphosphoryl)acetic acid (0.874 g, 4.46 mmol) and T3P (2.83 g, 4.46 mmol) were added. After 1 hour, the reaction was then partitioned between EtOAc (150 ml) and water (100 ml). The organic layer was separated, washed with brine (100 ml), dried over MgSO4, filtered and concentrated. The residue was purified by normal phase chromatography to give 227B (1.34 g, 95%). MS (ESI) m/z: 946/948 (M+H)+, bromine isotope.

Workup

  1. customTo a round bottom flask was
  2. waitAfter 4 hours
  3. waitAfter 1 hour
  4. customthe reaction was then partitioned between EtOAc (150 ml) and water (100 ml)
  5. customThe organic layer was separated
  6. washwashed with brine (100 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by normal phase chromatography

Sources & evidence

ORD record
ord-0e17d7bb401246539e3b6c59a87b6321
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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