Triethylamine → (+/-)-Methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester

HRID 1247644Notes

Reaction equation

HRID 1247644 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[N:16]=[C:15]3[N:17]([C:31]4[CH:32]=[C:33]([CH:36]=[CH:37][CH:38]=4)[C:34]#[N:35])[C:18](=[O:30])[N:19]([C:22]4[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=4)[CH:20]([CH3:21])[C:14]3=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1.C(N(CC)CC)C.[CH3:46][S:47](Cl)(=[O:49])=[O:48]>ClCCl>[C:34]([C:33]1[CH:32]=[C:31]([N:17]2[C:15]3[N:16]=[C:11]([NH:10][C:6]4[CH:5]=[C:4]([CH2:3][CH2:2][O:1][S:47]([CH3:46])(=[O:49])=[O:48])[CH:9]=[CH:8][CH:7]=4)[N:12]=[CH:13][C:14]=3[CH:20]([CH3:21])[N:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:18]2=[O:30])[CH:38]=[CH:37][CH:36]=1)#[N:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chloride2×HCID 9870839(+/-)-3-[7-[3-(2-hydroxy-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

Product 1

HCID 10325979(+/-)-Methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(±)-3-[7-[3-(2-Hydroxy-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile (0.67 mg; 1.27 mmol) (from Example 4 supra) was suspended in dichloromethane (13 mL). The mixture was treated with triethylamine (0.23 mL; 1.65 mmol) and methane-sulfonyl chloride (0.13 mL; 1.68 mmol) (Aldrich). The solid went into solution as the methanesulfonyl chloride was added. After 45 minutes, the reaction was shown by thin layer chromatography to be complete. The reaction was diluted with additional dichloromethane and washed with water and then brine. The organic phase was dried over anhydrous sodium sulfate, concentrated and dried under high vacuum to give crude (±)-methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester as a foam. This material was used in the next step without further purification. (Yield: 0.76 g, 95.4%).

Workup

  1. additionwas added
  2. washwashed with water
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-17b2dcb2cadb46ef8e160150f33a83d2
Source dataset
uspto-grants-2006_10
Patent number
US07129351B2

Reaction notes

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