Hydrochloric Acid → HCID 178467079, compound

HRID 2271679Notes

Reaction equation

HRID 2271679 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:18][CH2:17]1.[Cl:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([Cl:44])[C:30]=1[OH:45].Cl>ClCCl.CO>[ClH:28].[Cl:44][C:31]1[CH:32]=[C:33]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]3[NH:15][C@H:16]2[CH2:17][CH2:18][C@H:19]([CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH2:20][CH2:21]2)[CH:34]=[C:29]([Cl:28])[C:30]=1[OH:45]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 667151272,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 178467066HCID 178467066, compound

Product 1

HCID 178467079HCID 178467079, compoundYield 119%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Following general procedure F, 1-(6-bromo-4-(trans-4-(pyrrolidin-1-ylmethyl)cyclohexylamino)quinolin-3-yl)ethanone (6.0 g, 14.0 mmol) was reacted with 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (4.4 g, 15.0 mmol) to obtain the free base. The purified product was suspended in dichloromethane/methanol (1:1, 200 mL) after which HCl (35 mL, 1.25 M in methanol) was added to form a solution. The solution was concentrated to dryness and the resultant solid was triturated with dichloromethane. The mixture was filtered, washed with dichloromethane, and dried to obtain desired product (4.9 g, 60% over two steps) as a yellow solid: 1H NMR (300 MHz, CD3OD) δ 9.10 (s, 1H), 8.47 (d, J=2.1 Hz, 1H), 8.26 (dd, J=8.8, 1.8 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 7.73 (s, 2H), 4.55-4.45 (m, 1H), 3.70 (br s, 2H), 3.20-3.04 (m, 4H), 2.74 (s, 3H), 2.45 (d, J=12.6 Hz, 2H), 2.17-1.94 (m, 7H), 1.89-1.70 (m, 2H), 1.46-1.27 (m, 2H); APCI MS m/z 512 [C28H31Cl2N3O2+H]+; HPLC>99% (AUC), tR=8.69 min.

Workup

  1. customto obtain the free base
  2. additionwas added
  3. customto form a solution
  4. concentrationThe solution was concentrated to dryness
  5. customthe resultant solid was triturated with dichloromethane
  6. filtrationThe mixture was filtered
  7. washwashed with dichloromethane
  8. customdried

Sources & evidence

ORD record
ord-08e1f02670914fa3a8d6f4f0f0c772dd
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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