Hydrochloric Acid → HCID 117741034, compound

HRID 1775889Notes

Reaction equation

HRID 1775889 reaction equation
C(O[C:9]([NH:11][C@@H:12]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[N:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])=[CH:41][CH:40]=3)=[CH:35][N:34]=2)=[CH:29][CH:28]=1)[C:13]([N:15]1[CH2:18][CH:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)=[O:14])=[O:10])C1C=CC=CC=1.C([SiH]([CH2:58][CH3:59])CC)C.[CH2:60](N(CC)CC)C.CN(C(ON1N=N[C:77]2[CH:78]=[CH:79][CH:80]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN([CH:97]([CH3:99])[CH3:98])C(C)C.Cl>C(Cl)Cl.CN(C=O)C.C(O[Pd]OC(=O)C)(=O)C>[C:97]([C:59]1[CH:58]=[CH:77][C:78]([C:9]([NH:11][C@@H:12]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]3[N:38]=[CH:37][C:36]([C:39]4[CH:40]=[CH:41][C:42]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])=[CH:43][CH:44]=4)=[CH:35][N:34]=3)=[CH:31][CH:32]=2)[C:13]([N:15]2[CH2:16][CH:17]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:18]2)=[O:14])=[O:10])=[CH:79][CH:80]=1)([CH3:99])([CH3:60])[CH3:98]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117749005HCID 117749005, compound

Product 1

HCID 117741034HCID 117741034, compoundYield 265.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Prepared using General Procedures 18 and 7: To a stirred solution of (S)-tert-butyl 1-(2-(((benzyloxy)carbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate (708 mg, 1.00 mmol) and triethylsilane (352 μL, 2.20 mmol) in DCM (10 mL) was added a solution of diacetoxypalladium (22.5 mg, 0.100 mmol) and triethylamine (43 μL, 0.30 mmol) in DCM (2 mL). After 16 h, the mixture was filtered through Celite and solvents evaporated. The residue was taken up in DMF (6 mL) and the resulting solution added to a stirred solution of active ester prepared by the action of HATU (399 mg, 1.05 mmol) and DIEA (0.55 mL, 3.00 mmol) on 4-(tert-butyl)benzoic acid (196 mg, 1.10 mmol) in DMF (5 mL) over 10 min. After 1 h, the mixture was poured onto 0.5 M HCl (100 mL) and extracted with EA (3×50 mL). The combined organic extracts were washed with brine (20 mL), dried over MgSO4 and evaporated. Column chromatography (EA/DCM/iso-hexanes) gave 583 mg (80%) of tert-butyl (S)-1-(2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate. LCMS-ESI (m/z) calculated for C45H56N4O5: 732.4; no m/z observed, tR=3.99 min (Method 11).

Workup

  1. customPrepared
  2. filtrationthe mixture was filtered through Celite and solvents
  3. customevaporated
  4. additionthe resulting solution added to a stirred solution of active ester
  5. waitAfter 1 h
  6. extractionextracted with EA (3×50 mL)
  7. washThe combined organic extracts were washed with brine (20 mL)
  8. dry with materialdried over MgSO4
  9. customevaporated

Sources & evidence

ORD record
ord-4c705ddbcebf4f09af7b0b5495cdb173
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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