Thionyl Chloride → HCID 57670089, compound

HRID 1894448Notes

Reaction equation

HRID 1894448 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C:13]([N:15]2[C@@:19]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)([CH3:20])[C@@:18]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)([CH3:28])[N:17]=[C:16]2[C:36]2[CH:37]=[N:38][C:39]([C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:40][C:41]=2[O:42][CH2:43][CH3:44])=[O:14])[CH2:9]1)(C)(C)C.S(Cl)(Cl)=O>CO.FC(F)(F)C(O)=O>[NH2:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]([N:15]2[C@@:19]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=3)([CH3:20])[C@@:18]([C:29]3[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=3)([CH3:28])[N:17]=[C:16]2[C:36]2[CH:37]=[N:38][C:39]([C:45]([CH3:46])([CH3:48])[CH3:47])=[CH:40][C:41]=2[O:42][CH2:43][CH3:44])=[O:14])[CH2:9]1

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 57669953HCID 57669953, compound

Product 1

HCID 57670089HCID 57670089, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
77.5 °C

Procedure

{(S)-1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (12.6 mg, example 125) was diluted with methanol (1.5 mL) and trifluoroacetic acid (0.1 mL). The mixture was stirred at 75-80° C. for 1 h. Thionyl chloride (0.3 mL) was added dropwise and the mixture was stirred at 80° C. for 1 h. The mixture was then concentrated and diluted with methanol (2 mL) and neutralized with 15% solution of sodium hydroxide. Purification of the crude product on a preparative HPLC (reversed phase, eluting with acetonitrile and water) gave the title product as a mixture of diastereomers (5.4 mg). HR-MS (ES, m/z) calculated for C33H40Cl2N5O2 [(M+H)+] 608.2554, observed 608.2554.

Workup

  1. stirringthe mixture was stirred at 80° C. for 1 h
  2. concentrationThe mixture was then concentrated
  3. additiondiluted with methanol (2 mL)
  4. customPurification of the crude product
  5. washon a preparative HPLC (reversed phase, eluting with acetonitrile and water)

Sources & evidence

ORD record
ord-294733bbb981458b958680cd22a03abf
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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