Morpholine → HCID 58346527, compound

HRID 222042Notes

Reaction equation

HRID 222042 reaction equation
CS(O[CH2:6][CH2:7][N:8]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13]3[C:19]4[C:20]([NH:24][C:25]5[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]6[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=6)=[C:27]([Cl:39])[CH:26]=5)=[N:21][CH:22]=[N:23][C:18]=4[S:17][C:14]=32)=[N:9]1)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.C(N(C(C)C)CC)(C)C>CC#N>[CH2:32]([O:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:20]2[N:21]=[CH:22][N:23]=[C:18]3[S:17][C:14]4[C:15]5[C:10]([CH2:11][CH2:12][C:13]=4[C:19]=23)=[N:9][N:8]([CH2:7][CH2:6][N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH:16]=5)=[CH:26][C:27]=1[Cl:39])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 58346430HCID 58346430, compound

Product 1

HCID 58346527HCID 58346527, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To CH3CN (4 mL) were sequentially added 2-(6-{[4-(benzyloxy)-3-chlorophenyl]amino}-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl)ethyl methanesulfonate (85 mg, 0.15 mmol), morpholine (0.04 mL, 0.44 mmol), and diisopropylethylamine (0.05 mL, 0.29 mmol). The mixture was stirred at 70° C. for 16 h after which time the mixture was removed from heating, and allowed to cool to rt. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were concentrated under reduced pressure and purified by prep HPLC. The combined fractions were treated with saturated Na2CO3 and dried to afford free base product (35 mg, 42%) as a white solid. 1H-NMR (DMSO-d6) δ 8.42 (s, 1H), 8.25 (s, 1H), 7.93 (s, 1H), 7.72 (d, 1H), 7.33-7.49 (m, 6H), 7.18 (d, 1H), 5.19 (s, 2H), 4.18 (t, 2H), 3.55 (m, 4H), 3.39 (t, 2H), 2.89 (t, 2H), 2.71 (t, 2H), 2.42 (m, 4H); LCMS RT=1.98 min, [M+H]+=573.4.

Workup

  1. customwas removed
  2. temperaturefrom heating
  3. temperatureto cool to rt
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. concentrationThe combined organic layers were concentrated under reduced pressure
  7. custompurified by prep HPLC
  8. additionThe combined fractions were treated with saturated Na2CO3
  9. customdried

Sources & evidence

ORD record
ord-c006f1e267544d9f917005abea350640
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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