1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-Chloro-5-({7-[(2E)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenol

HRID 38609

Reaction equation

HRID 38609 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.Cl.[CH:9]12[O:16][CH:13]([CH2:14][CH2:15]1)[CH2:12][NH:11][CH2:10]2.CCN(C(C)C)C(C)C.Cl.[Cl:27][C:28]1[CH:29]=[C:30]([OH:48])[CH:31]=[C:32]([NH:34][C:35]2[C:36]3[C:43]4[CH2:44][CH2:45][NH:46][CH2:47][C:42]=4[S:41][C:37]=3[N:38]=[CH:39][N:40]=2)[CH:33]=1.CCN=C=NCCCN(C)C>C(Cl)Cl.O>[Cl:27][C:28]1[CH:29]=[C:30]([OH:48])[CH:31]=[C:32]([NH:34][C:35]2[C:36]3[C:43]4[CH2:44][CH2:45][N:46]([C:5](=[O:7])/[CH:4]=[CH:3]/[CH2:2][N:11]5[CH2:10][CH:9]6[O:16][CH:13]([CH2:14][CH2:15]6)[CH2:12]5)[CH2:47][C:42]=4[S:41][C:37]=3[N:38]=[CH:39][N:40]=2)[CH:33]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2×HCID 64364114-Bromocrotonic acidHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 668500883-Chloro-5-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride

Product 1

HCID 252209953-Chloro-5-({7-[(2E)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenolYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(2E)-4-Bromobut-2-enoic acid (168 mg, 0.81 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (130 mg, 0.87 mmol) were dissolved in DCM (2.0 mL). DIPEA (210 mg, 1.62 mmol) was added, and the mixture was stirred at rt for 2 h. Subsequently, 3-chloro-5-(5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride from Example 65A (200 mg, 0.54 mmol), EDCI (104 mg, 0.54 mmol) and DIPEA (140 mg, 1.08 mmol) were added, and the mixture was stirred at rt overnight. Then, the reaction mixture was diluted with water, and after separation the organic layer was washed with water. The solvent was removed in vacuo, and the crude product was purified by preparative HPLC to yield 106 mg (38%) of the title compound.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. customafter separation the organic layer
  3. washwas washed with water
  4. customThe solvent was removed in vacuo
  5. customthe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-7fe8481a264b4bb6bd83a21b1f49cf7b
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Linked notes

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