Acetic Acid → 3-{4-[4-(1H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzylamino}-propionic acid methyl ester

HRID 2297767Notes

Reaction equation

HRID 2297767 reaction equation
[CH3:1][O:2][C:3](=[O:7])[CH2:4][CH2:5][NH2:6].C(O)(=O)C.[NH:12]1[C:20]2[C:15](=[CH:16][C:17]([NH:21][C:22]3[C:23]4[S:30][C:29]([C:31]5[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=5)=[CH:28][C:24]=4[N:25]=[CH:26][N:27]=3)=[CH:18][CH:19]=2)[CH:14]=[CH:13]1.C([BH3-])#N.[Na+]>CO.C(Cl)(Cl)Cl.O>[CH3:1][O:2][C:3](=[O:7])[CH2:4][CH2:5][NH:6][CH2:35][C:34]1[CH:33]=[CH:32][C:31]([C:29]2[S:30][C:23]3[C:22]([NH:21][C:17]4[CH:16]=[C:15]5[C:20](=[CH:19][CH:18]=4)[NH:12][CH:13]=[CH:14]5)=[N:27][CH:26]=[N:25][C:24]=3[CH:28]=2)=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 192794Methyl beta-alanateHCID 5003444Sodium cyanoborohydrideHCID 183827594-(4-(1H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzaldehyde

Product 1

HCID 543909063-{4-[4-(1H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzylamino}-propionic acid methyl esterYield 66.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

3-Amino-propionic acid methyl ester (261 mg, 1.7 mmol) was dissolved in 3 mL of methyl alcohol and the pH was adjusted to 6 with concentrated acetic acid. 4-[4-(1H-Indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzaldehyde (100 mg, 0.28 mmol) was added to the solution followed by sodium cyanoborohydride (11 mg, 0.17 mmol). After 14 hours the reaction mixture was poured into water and diluted with chloroform. The aqueous layer was separated and the pH was adjusted to 8.5 with 1N sodium hydroxide. The desired product was extracted from the aqueous layer with chloroform (3×20 mL), the combined organic extracts were dried over sodium sulfate, filtered, and dried in vacuo to afford 85 mg (41%) of 3-{4-[4-(1H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzylamino}-propionic acid methyl ester. The product was converted to the HCl salt by stirring with 1 equivalent of 1N HCl in ether and the resulting yellow solid was dried in vacuo. M.P. 105-118° C.; LC-MS: 458 (MH+); HPLC RT: 3.86 minutes.

Workup

  1. customThe aqueous layer was separated
  2. extractionThe desired product was extracted from the aqueous layer with chloroform (3×20 mL)
  3. dry with materialthe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customdried in vacuo

Sources & evidence

ORD record
ord-9b50fa9a2cf448fab056bd826473db43
Source dataset
uspto-grants-2002_12
Patent number
US06492383B1

Reaction notes

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