Water → 4-(5-Cyano-7-cyclopropyl-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

HRID 2093646Notes

Reaction equation

HRID 2093646 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:36]=[CH:35][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][N:22]([C:25]5[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=[C:4]([C:37]#[N:38])[CH:3]=1.[CH:39]1(B(O)O)[CH2:41][CH2:40]1.C(=O)([O-])[O-].[K+].[K+].O>C(COC)OC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:37]([C:4]1[CH:3]=[C:2]([CH:39]2[CH2:41][CH2:40]2)[C:10]2[O:9][C:8]([C:11]3[CH:36]=[CH:35][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][N:22]([C:25]5[N:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=1)#[N:38]

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 687430814-(7-Bromo-5-cyano-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

Product 1

HCID 251726704-(5-Cyano-7-cyclopropyl-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(7-bromo-5-cyano-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide (EXAMPLE 113, Step A) (59 mg, 0.10 mmol), cyclopropylboronic acid (86 mg, 1.0 mmol), potassium carbonate (138 mg, 1.0 mmol), and tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol) in dimethoxyethane (7 ml)/water (0.7 ml) was heated to reflux and stirred at this temperature for 4 d. The mixture was diluted with ethyl acetate, filtered, and concentrated. The residue was purified by flash column chromatography to afford the title compound. Mass spectrum (ESI) 547.2 (M+1). 1H NMR (500 MHz, DMSO-d6) δ: 8.77 (t, J=5.5 Hz, 1H), 8.65 (d, J=4.8 Hz, 1H), 8.31 (d, J=8.2 Hz, 2H), 8.18 (s, 1H), 8.08 (d, J=8.3 Hz, 2H), 7.56 (s, 1H) 6.96 (d, J=4.8 Hz, 1H), 5.74 (s, 1H), 4.65 (br d, J=12.6 Hz, 2H), 3.22 (t, J=6.2 Hz, 2H), 2.95 (t, J=12.4 Hz, 2H), 2.40 (m, 1H), 1.93 (m, 1H), 1.81 (br d, J=11.9 Hz, 2H), 1.15 (m, 5H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-636fc8ed79d44f4082ea135d95052dcc
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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