Acetic Acid → HCID 57794534, compound

HRID 2099379Notes

Reaction equation

HRID 2099379 reaction equation
[BH3-][C:2]#[N:3].[Na+].N[C@H:6]([C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:27]=[C:26]3[C:21]([C:22]([NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=4[F:36])=[N:23][CH:24]=[N:25]3)=[CH:20][C:19]=2[O:37][CH3:38])[CH2:13][CH2:12]1)=[O:10])[CH2:7][OH:8].O.O.O.[C:42]([O-])(=O)C.[Na+].C=O.C(O)(=O)C>>[Cl:35][C:31]1[C:30]([F:36])=[C:29]([CH:34]=[CH:33][CH:32]=1)[NH:28][C:22]1[C:21]2[C:26](=[CH:27][C:18]([O:17][CH:14]3[CH2:15][CH2:16][N:11]([C:9](=[O:10])[C@@H:6]([N:3]([CH3:2])[CH3:42])[CH2:7][OH:8])[CH2:12][CH2:13]3)=[C:19]([O:37][CH3:38])[CH:20]=2)[N:25]=[CH:24][N:23]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 23665404Sodium Acetate TrihydrateHCID 68903110HCID 68903110, compound

Product 1

HCID 57794534HCID 57794534, compoundYield 26%

Procedure

Solid NaCNBH3 (38.3 mg, 0.614 mmol) was added to a stirred solution of (2S)-2-amino-3-[4-({4-[3-chloro-2-fluoroanilino]-6-methoxyquinazolin-7-yl}oxy)piperidin-1-yl]-3-oxopropan-1-ol (150 mg, 0.307 mmol, Example 15), sodium acetate trihydrate (251 mg, 3.07 mmol), formaldehyde 37% (aq) (2.5 ml) and acetic acid (184 mg, 3.07 mmol) at 0-5° C. The resulting solution was allowed to warm to room temperature and stir for 1 hour. The mixture was then evaporated and the resulting yellow residue was purified by flash chromatography on silica gel eluting with increasingly polar mixtures of dichloromethane/7N ammonia in methanol (100/0-85/15). Fractions containing the desired product were combined and evaporated to give the title compound as a white solid (26%); 1H NMR Spectrum: 1.52-1.69 (m, 2H), 1.94-2.07 (m, 2H), 2.28-2.30 (2 x s, 6H), 3.15-3.22 (m, 2H), 3.53-3.76 (m, 4H), 3.94 (s, 3H), 4.02 (m, 1H), 4.49 (m, 1H), 4.92-4.94 (m, 1H), 7.27(dd, 1H), 7.34 (s, 1H), 7.47 (dd, 1H), 7.51 (dd, 1H), 7.81 (s, 1H), 8.38 (s, 1H), 9.65 (s, 1H); Mass Spectrum: (M+H)+ 518.

Workup

  1. customThe mixture was then evaporated
  2. customthe resulting yellow residue was purified by flash chromatography on silica gel eluting
  3. temperaturewith increasingly polar mixtures of dichloromethane/7N ammonia in methanol (100/0-85/15)
  4. additionFractions containing the desired product
  5. customevaporated

Sources & evidence

ORD record
ord-0dbb1b4d9d7942d6bccf7ba2e0fc3a1b
Source dataset
uspto-grants-2009_08
Patent number
US07569577B2

Reaction notes

Loading…