Trifluoroacetic acid → HCID 178426861, compound

HRID 929105Notes

Reaction equation

HRID 929105 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][C:9]1[CH:46]=[C:45]([CH3:47])[CH:44]=[CH:43][C:10]=1[O:11][CH2:12][C@H:13]([OH:42])[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][NH:19][C:18](=[O:22])[C:17]=1[C:23]1[NH:34][C:33]2[C:25](=[CH:26][C:27]3[CH2:28][N:29]([CH:36]4[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[C:30](=[O:35])[C:31]=3[CH:32]=2)[N:24]=1.[CH:48]1([CH:51]=O)[CH2:50][CH2:49]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.O.CC#N>[CH:48]1([CH2:51][N:39]2[CH2:38][CH2:37][CH:36]([N:29]3[CH2:28][C:27]4[CH:26]=[C:25]5[C:33]([NH:34][C:23]([C:17]6[C:18](=[O:22])[NH:19][CH:20]=[CH:21][C:16]=6[NH:15][CH2:14][C@@H:13]([OH:42])[CH2:12][O:11][C:10]6[CH:43]=[CH:44][C:45]([CH3:47])=[CH:46][C:9]=6[CH3:8])=[N:24]5)=[CH:32][C:31]=4[C:30]3=[O:35])[CH2:41][CH2:40]2)[CH2:50][CH2:49]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 1784268602-(4-[(R)-3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl)-6-piperidin-4-yl-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one

Product 1

HCID 178426861HCID 178426861, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the TFA salt of 2-{4-[(R)-3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-piperidin-4-yl-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one (40 mg, 0.061 mmol) and cyclopropanecarbaldehyde (150 μL, 2.0 mmol) in a mixed solvent of CH3CN (6 mL) and H2O (2 mL) was added AcOH (500 μL) at 0° C. and the resulting reaction mixture was stirred at 0° C. for 20 min and followed by addition of Na(OAc)3BH (254 mg, 1.2 mmol). The reaction mixture was stirred at 0° C. for 1 h and at the room temperature for 1 h and then evaporated. The residue was subjected to HPLC purification to afford the title compound in TFA salt form. 1H NMR (DMSO-d6) δ 0.39 (m, 2H), 0.67 (m, 2H), 1.10 (m, 1H), 2.03 (m, 2H), 2.12 (m, 2H), 2.19 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.01 (m, 2H), 3.18 (m, 2H), 3.50-4.15 (7H), 4.32 (m, 1H), 4.47 (s, 2H), 6.22 (d, J=7 Hz, 1H), 6.80 (d, J=7 Hz, 1H), 6.91 (d, J=7 Hz, 1H), 6.97 (s, 1H), 7.38 (d, J=7 Hz, 1H), 7.57 (br s, 1H), 7.82 (br s, 1H), 11.13 (br s, 1H, NH), 11.22 (br d, J=6 Hz, 1H, NH); ESI-MS m/z 597.3 (MH+).

Workup

  1. customthe resulting reaction mixture
  2. stirringThe reaction mixture was stirred at 0° C. for 1 h and at the room temperature for 1 h
  3. customevaporated
  4. customThe residue was subjected to HPLC purification

Sources & evidence

ORD record
ord-e62e64a521b14091a3ef0af2edee3cf0
Source dataset
uspto-grants-2016_03
Patent number
US09290503B2

Reaction notes

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