Diisopropylethylamine → (S)-methyl 2-(2-((2-(allyloxy)benzyl)carbamoyl)-5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HRID 1481973Notes

Reaction equation

HRID 1481973 reaction equation
[Na+].[CH2:2]([C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]3[CH:18]=[C:19]([C:21]([O-])=[O:22])[N:20]=[C:16]3[CH:15]=[C:14]([CH3:24])[C:13]=2[C@H:25]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C:26]([O:28][CH3:29])=[O:27])[CH2:8][CH2:7]1)[CH2:3][CH:4]=[CH2:5].[CH2:36]([O:39][C:40]1[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=1[CH2:42][NH2:43])[CH:37]=[CH2:38].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH2:36]([O:39][C:40]1[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=1[CH2:42][NH:43][C:21]([C:19]1[N:20]=[C:16]2[CH:15]=[C:14]([CH3:24])[C:13]([C@H:25]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])[C:26]([O:28][CH3:29])=[O:27])=[C:12]([N:9]3[CH2:10][CH2:11][C:6]([CH2:2][CH2:3][CH:4]=[CH2:5])([CH3:35])[CH2:7][CH2:8]3)[N:17]2[CH:18]=1)=[O:22])[CH:37]=[CH2:38]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14940440[2-(Prop-2-en-1-yloxy)phenyl]methanamineHCID 118308860(S)-5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid sodium salt

Product 1

HCID 118308904(S)-methyl 2-(2-((2-(allyloxy)benzyl)carbamoyl)-5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A yellow solution of (S)-5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid sodium salt (40 mg, 0.081 mmol, 1 equiv), 2-allyloxybenzylamine (18 mg, 0.113 mmol, 1.4 equiv), DIPEA (0.042 mL, 0.243 mmol, 3 equiv), and HATU (43 mg, 0.113 mmol, 1.4 equiv) in DMF (0.81 mL) was stirred 2 h. The reaction was then diluted with EtOAc, washed with saturated aqueous NaHCO3, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc/hex) to provide the product (30 mg, 60%) as a colorless oil. 1H NMR (400 MHz, CDCl3) [note: appears to be at least two rotamers, only major rotamer transcribed] δ 8.21 (s, 1H), 7.81 (t, J=6.1 Hz, 1H), 7.26-7.16 (m, 2H), 6.97-6.85 (m, 2H), 6.19-6.06 (m, 2H), 5.93-5.82 (m, 1H), 5.47 (dq, J=17.3, 1.5 Hz, 1H), 5.31 (dq, J=10.5, 1.4 Hz, 1H), 5.14-4.95 (m, 2H), 4.72 (d, J=6.0 Hz, 2H), 4.63 (dt, J=5.0, 1.5 Hz, 2H), 3.70 (s, 3H), 3.61-3.48 (m, 2H), 3.07 (d, J=13.8 Hz, 1H), 2.85 (d, J=12.0 Hz, 1H), 2.45 (d, J=1.0 Hz, 3H), 2.17-2.07 (m, 2H), 1.71-1.40 (m, 6H), 1.24 (s, 9H), 1.13 (s, 3H); LCMS (ESI, M+1): 617.4.

Workup

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography (0-100% EtOAc/hex)

Sources & evidence

ORD record
ord-e9f2df51c46d4a1a9037b38526d004cd
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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