Trifluoroacetic acid → Sodium 2-(4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzamido)-2-methylpropyl phosphate

HRID 884017Notes

Reaction equation

HRID 884017 reaction equation
C([O:5][P:6]([O:13][CH2:14][C:15]([NH:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([S:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34]C(=O)OC(C)(C)C)=[CH:30][CH:29]=2)=[C:23]([NH:42][C:43]2[C:44]3[CH:52]=[CH:51][C:50]([CH:53]([CH3:55])[CH3:54])=[N:49][C:45]=3[N:46]=[CH:47][N:48]=2)[CH:22]=1)=[O:20])([CH3:17])[CH3:16])([O:8]C(C)(C)C)=[O:7])(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+:67]>ClCCl>[P:6]([O-:7])([O-:8])([O:13][CH2:14][C:15]([NH:18][C:19](=[O:20])[C:21]1[CH:26]=[CH:25][C:24]([S:27][C:28]2[CH:29]=[CH:30][C:31]([NH2:34])=[CH:32][CH:33]=2)=[C:23]([NH:42][C:43]2[C:44]3[CH:52]=[CH:51][C:50]([CH:53]([CH3:54])[CH3:55])=[N:49][C:45]=3[N:46]=[CH:47][N:48]=2)[CH:22]=1)([CH3:17])[CH3:16])=[O:5].[Na+:67].[Na+:67]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 67041161Tert-butyl 4-(4-(1-(di-tert-butoxyphosphoryloxy)-2-methylpropan-2-ylcarbamoyl)-2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenylthio)phenylcarbamate

Product 1

HCID 67040578Sodium 2-(4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzamido)-2-methylpropyl phosphateYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 95D (90 mg, 0.11 mmol) in dichloromethane (0.5 mL) was reacted with trifluoroacetic acid [TFA] (0.5 mL) dropwise at room temperature then stirred for 1 hour. The reaction was concentrated and re-dissolved in a mixture of methanol and water to which was added sodium hydrogencarbonate (0.10 g, 1.19 mmol). Purification of the residue on a reverse phase C18 column eluting with a gradient of methanol in water (0-100%) gave the title compound as a yellow solid (62.5 mg, 88%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.29 (d, J=6.99 Hz, 6 H) 1.32 (s, 6 H) 3.03-3.20 (m, 1 H) 3.54 (d, J=11.40 Hz, 2 H) 5.45 (s, 2 H) 6.50-6.53 (m, 1 H) 6.62 (d, J=8.46 Hz, 2 H) 7.11 (d, J=8.46 Hz, 2 H) 7.34 (s, 1 H) 7.60 (s, 1 H) 7.87 (s, 1 H) 8.29 (s, 1 H) 8.74 (s, 1 H) 9.82 (s, 1 H).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionre-dissolved in a mixture of methanol and water to which
  3. customPurification of the residue on a reverse phase C18 column
  4. washeluting with a gradient of methanol in water (0-100%)

Sources & evidence

ORD record
ord-dc358ed3b5364029bf7e99ae48d22b7a
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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