Acetic Anhydride → HCID 16718742, compound

HRID 1916345Notes

Reaction equation

HRID 1916345 reaction equation
[C:1](O)(C(F)(F)F)=O.C(Cl)Cl.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[S:26][C:25]3[C:24](=[O:27])[N:23]([C:28]4[CH:44]=[CH:43][C:31]([O:32][CH2:33][CH2:34][NH:35][C:36](=O)[O:37]C(C)(C)C)=[C:30]([O:45][CH3:46])[CH:29]=4)[CH:22]=[N:21][C:20]=3[CH:19]=2)=[CH:14][CH:13]=1.CC(OC(C)=O)=O.CCN(CC)CC>C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[S:26][C:25]3[C:24](=[O:27])[N:23]([C:28]4[CH:44]=[CH:43][C:31]([O:32][CH2:33][CH2:34][NH:35][C:36](=[O:37])[CH3:1])=[C:30]([O:45][CH3:46])[CH:29]=4)[CH:22]=[N:21][C:20]=3[CH:19]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 16718701HCID 16718701, compoundHCID 21863450Trifluoroacetic acid methylene chloride

Product 1

HCID 16718742HCID 16718742, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A 10% TFA/CH2Cl2 solution (0.5 mL) containing tert-butyl 2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-ethylcarbamate (15 mg, 0.03 mmol) (Example 3) was stirred for 2.5 hr whereupon the volatiles were removed under vacuum. To the residue containing 3-(4-(2-aminoethoxy)-3-methoxyphenyl)-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one was sequentially added CH2Cl2 (0.25 mL), Ac2O (20 mg, 0.2 mmol) and Et3N (74 mg, 0.7 mmol). After standing overnight, the reaction was diluted with aq Na2CO3 and extracted 4× with CH2Cl2. The combined organic layers were washed with brine and dried over Na2SO4. After removal of the solvent the residue was chromatographed on silica gel using 5-10% MeOH/EtOAc to elute the desired acetamide (12 mg). 1H NMR (CDCl3) δ 2.03 (s, 3H), 3.72 (m, 2H), 3.91 (s, 3H), 4.16 (t, 2H, J=4.8 Hz), 6.13 (m, 1H), 6.94 (dd, 1H, J=8.4 Hz, J=2.2 Hz), 6.98 (d, 1H, J=2.2 Hz), 7.02 (d, 1H, J=8.4 Hz), 7.45 (d, 2H, JAB=8.7 Hz), 7.54 (s, 1H), 7.66 (d, 2H, JAB=8.7 Hz), 8.14 (s, 1H); HPLC (Method #1): 3.67 min; LCMS m/z: 498 [M+H].

Workup

  1. customwere removed under vacuum
  2. additionTo the residue containing 3-(4-(2-aminoethoxy)-3-methoxyphenyl)-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one
  3. waitAfter standing overnight
  4. extractionextracted 4× with CH2Cl2
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. customAfter removal of the solvent the residue
  8. customwas chromatographed on silica gel using 5-10% MeOH/EtOAc
  9. washto elute the desired acetamide (12 mg)
  10. custom3.67 min

Sources & evidence

ORD record
ord-975373ea0c374ee3ad4585d5ba5109b8
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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