Trifluoroacetic acid → HCID 117748975, compound

HRID 1775893Notes

Reaction equation

HRID 1775893 reaction equation
[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][C@@H:13]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:39]=[CH:38][C:37]([C:40]4[CH:45]=[CH:44][C:43]([O:46][CH2:47][CH2:48][CH2:49][CH:50]([CH3:52])[CH3:51])=[CH:42][CH:41]=4)=[CH:36][N:35]=3)=[CH:30][CH:29]=2)[C:14]([N:16]2[CH2:19][CH:18]([C:20]([O:22]C(C)(C)C)=[O:21])[CH2:17]2)=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][C@@H:13]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:39]=[CH:38][C:37]([C:40]4[CH:45]=[CH:44][C:43]([O:46][CH2:47][CH2:48][CH2:49][CH:50]([CH3:52])[CH3:51])=[CH:42][CH:41]=4)=[CH:36][N:35]=3)=[CH:30][CH:29]=2)[C:14]([N:16]2[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[CH2:17]2)=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117748921HCID 117748921, compound

Product 1

HCID 117748975HCID 117748975, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 8: To a stirred solution of tert-butyl (S)-1-(2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-((4-methylpentyl)oxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate (188 mg, 0.26 mmol), in DCM (2 mL) was added TFA (2 mL). The mixture was stirred for 4 h then concentrated. The resulting solid was dissolved in DCM (10 mL) and concentrated (5×) to remove excess TFA, affording 169 mg (98%) of 1-(2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-((4-methylpentyl)oxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylic acid 798 as a yellow solid. LCMS-ESI (m/z) calculated for C38H44N4O5S: 668.85. found 669.3 [M+H]+, tR=9.121 min (Method 16). 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 2H), 8.12 (d, J=7.8 Hz, 2H), 7.58 (m, 3H), 7.45 (m, 1H), 7.42 (m, 2H), 7.06 (m, 2H), 6.84 (m, 1H), 4.71 (d, J=7.7 Hz, 1H), 4.33-4.14 (m, 2H), 4.08 (dd, J=19.8, 9.1 Hz, 2H), 4.03 (t, J=6.6 Hz, 2H), 3.30 (dd, J=12.5, 4.2 Hz, 1H), 3.06 (t, J=11.9 Hz, 1H), 2.91 (s, 1H), 1.91-1.76 (m, 2H), 1.64 (dt, J=13.0, 6.6 Hz, 1H), 1.43-1.33 (m, 11H), 0.95 (d, J=6.6 Hz, 6H).

Workup

  1. customPrepared
  2. concentrationthen concentrated
  3. dissolutionThe resulting solid was dissolved in DCM (10 mL)
  4. concentrationconcentrated (5×)
  5. customto remove excess TFA

Sources & evidence

ORD record
ord-155fe3cc0b4b4449821dc52f96f11433
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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