Sodium Hydroxide → alisertib sodium anhydrous

HRID 912599Notes

Reaction equation

HRID 912599 reaction equation
[Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[C:6]3[N:23]=[C:22]([NH:24][C:25]4[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[C:27]([O:34][CH3:35])[CH:26]=4)[N:21]=[CH:20][C:7]=3[CH2:8][N:9]=[C:10]([C:11]3[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=3[F:19])[C:4]=2[CH:3]=1.[OH-].[Na+:39]>C(O)C.O>[Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[C:6]3[N:23]=[C:22]([NH:24][C:25]4[CH:33]=[CH:32][C:28]([C:29]([O-:31])=[O:30])=[C:27]([O:34][CH3:35])[CH:26]=4)[N:21]=[CH:20][C:7]=3[CH2:8][N:9]=[C:10]([C:11]3[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=3[F:19])[C:4]=2[CH:3]=1.[Na+:39]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 24771867Alisertib

Product 1

HCID 66819785alisertib sodium anhydrousYield 86.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a stirred suspension of 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid (98.0 g, 190 mmol) in ethanol (2.0 L) was added 1.044 M Sodium hydroxide in water (199 mL). The resultant homogeneous solution was stirred for 1 hour, during which time a thick precipitate formed. The product was collected by filtration, and washed with ethanol (0.5 L) and diethyl ether (1.0 L). The resultant solid was dried in vacuo at 60-70° C. for 4 days to provide 88.6 g (86.8%) of sodium 4-([9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino)-2-methoxybenzoate as a light tan solid, mp 225° C. (decomp). 1H NMR (DMSO-d6) δ 9.86 (s, 1H), 8.60 (s, 1H), 8.29 (d, 1H), 7.79 (dd, 1H), 7.60 (br s, 1H), 7.40 (dd, 1H), 7.29 (d, 1H), 7.25-7.15 (m, 2H), 6.9 (br s, 2H), 4.9 (br s, 1H), 3.8 (br s, 1H), 3.70 (s, 3H), 3.35 (br s, 3H); MS m/z 519 (M+−Na+H, 100%); CHN Anal. Calcd. for C27H19ClFN4NaO40.33 EtOH−1.3H2O: C, 57.33; H, 4.10; N, 9.67. Found: C, 57.14; H, 3.99; N, 9.65.

Workup

  1. customformed
  2. filtrationThe product was collected by filtration
  3. washwashed with ethanol (0.5 L) and diethyl ether (1.0 L)
  4. customThe resultant solid was dried in vacuo at 60-70° C. for 4 days

Sources & evidence

ORD record
ord-59a2bd6271ae4c5383e12b05c264d617
Source dataset
uspto-grants-2011_09
Patent number
US08026246B2

Reaction notes

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