Diethanolamine → HCID 72202008, compound

HRID 629087Notes

Reaction equation

HRID 629087 reaction equation
Br[C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[NH:23]([CH2:27][CH2:28][OH:29])[CH2:24][CH2:25][OH:26].CCN(C(C)C)C(C)C.[N:39]1[CH:44]=[C:43](B(O)O)[CH:42]=[N:41][CH:40]=1>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC.CC(O)C>[OH:26][CH2:25][CH2:24][NH:23][CH2:27][CH2:28][O:29][C:3]1[C:2]([C:43]2[CH:44]=[N:39][CH:40]=[N:41][CH:42]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1

Participants

9

Reactant 4

HCID 8113Diethanolamine2×HCID 81531DiisopropylethylamineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 72202008HCID 72202008, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 44.2, 60 mg, 0.152 mmol), diethanolamine (19.14 mg, 0.182 mmol), DIPEA (53.0 μl, 0.303 mmol) and iPrOH (150 μl) were added to a vial, which was sealed and subjected to MW irradiation at 110° C. for 60 min, and then at 150° C. for 10 min. Diethanolamine (15.95 mg, 0.152 mmol) was then added and the RM was subjected to MW irradiation at 160° C. for 1 h. Pyrimidin-5-ylboronic acid (56.4 mg, 0.455 mmol), Pd(PPh3)2Cl2 (10.65 mg, 0.015 mmol) Na2CO3 (80 mg, 0.758 mmol) water (200 μL) and DME (600 μL)—were then added and the vial was resealed and stirred at 80° C. for 2.5 h. The RM was diluted with 1.5 mL of THF, stirred with Si-Thiol (Silicycle, 59.7 mg, 0.076 mmol) for 1 h, filtrated and the filtrate was evaporated to dryness under reduced pressure to give a residue which was purified by preparative HPLC (Condition 8, 20% for 0.2 min then 20% to 50% in 12 min) to yield the title compound as a white solid. UPLC-MS (Condition 1) tR=1.59 min, m/z=464.0 [M+H]+, m/z=462.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.83 (t, J=5.4 Hz, 2H) 3.18 (t, 2H) 3.53 (t, J=5.4 Hz, 2H) 4.61 (t, J=5.4 Hz, 2H) 4.90 (br. s, 1H) 7.40 (d, J=8.6 Hz, 2H) 7.88 (d, J=4.6 Hz, 2H) 8.52 (d, J=2.4 Hz, 1H) 8.84 (d, J=2.4 Hz, 1H) 9.20 (s, 2H) 9.23 (s, 1H) 10.49 (s, 1H).

Workup

  1. customwas sealed
  2. customsubjected to MW irradiation at 110° C. for 60 min
  3. customthe RM was subjected to MW irradiation at 160° C. for 1 h
  4. filtrationfiltrated
  5. customthe filtrate was evaporated to dryness under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative HPLC (Condition 8, 20% for 0.2 min

Sources & evidence

ORD record
ord-e8734446835e47c2b271fd85e2511f31
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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