Diisopropylethylamine → (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(5-(dimethylcarbamoyl)-1H-pyrrol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

HRID 525747Notes

Reaction equation

HRID 525747 reaction equation
Cl[C:2]1[C:21]([C:22]2[NH:23][C:24]([C:27](=[O:31])[N:28]([CH3:30])[CH3:29])=[CH:25][CH:26]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH:32]1[CH2:36][CH2:35][C@@H:34]([OH:37])[CH2:33]1.CCN(C(C)C)C(C)C>CC(O)C>[Cl:19][C:16]([F:17])([F:18])[O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:20]=[C:21]([C:22]3[NH:23][C:24]([C:27](=[O:31])[N:28]([CH3:30])[CH3:29])=[CH:25][CH:26]=3)[C:2]([N:32]3[CH2:36][CH2:35][C@@H:34]([OH:37])[CH2:33]3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 899079936-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(5-(dimethylcarbamoyl)-1H-pyrrol-2-yl)nicotinamide

Product 1

HCID 89908237(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(5-(dimethylcarbamoyl)-1H-pyrrol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(5-(dimethylcarbamoyl)-1H-pyrrol-2-yl)nicotinamide (Stage 73.1, 60 mg, 0.102 mmol), (R)-pyrrolidin-3-ol (17.82 mg, 0.205 mmol), DIPEA (71.5 μL, 0.409 mmol) and iPrOH (205 μL) in a sealed vial was subjected to MW irradiation at 140° C. for 1 h. The RM was purified by preparative SFC (Column NH2, isocratic 24% in 6 min.) to yield the title compound as a white solid. UPLC-MS (Condition 3) tR=1.03 min, m/z=520.1 [M+H]+, m/z=564.2 [M+FA−H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.69-1.78 (m, 1H) 1.78-1.89 (m, 1H) 2.96 (d, J=11.74 Hz, 1H) 3.13 (br. s, 6H) 3.25-3.31 (m, 2H) 3.38-3.51 (m, 1H) 4.20 (br. s, 1H) 4.86 (d, J=2.57 Hz, 1H) 6.11-6.21 (m, 1H) 6.57-6.66 (m, 1H) 7.33 (d, J=9.17 Hz, 2H) 7.82-7.92 (m, 2H) 8.04 (d, J=2.45 Hz, 1H) 8.71 (d, J=2.45 Hz, 1H) 10.15 (s, 1H) 11.66 (br. s, 1H).

Workup

  1. customvial was subjected to MW irradiation at 140° C. for 1 h
  2. customThe RM was purified by preparative SFC (Column NH2, isocratic 24% in 6 min.)

Sources & evidence

ORD record
ord-d9825d2a92d54b3aa131c886b94c1d9b
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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