Triethylamine → HCID 118216034, compound

HRID 61404Notes

Reaction equation

HRID 61404 reaction equation
Cl.[CH2:2]([C@H:5]1[CH2:9][NH:8][CH2:7][C@@:6]1([N:22]=[N+:23]=[N-:24])[C:10]([O:12][CH2:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:11])[CH:3]=[CH2:4].[C:25]([O:29][C:30]([N:32]1[CH:41]([C:42](O)=[O:43])[CH2:40][C:39]2[C:34](=[CH:35][C:36]([Cl:45])=[CH:37][CH:38]=2)[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].CCN(CC)CC.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>C(Cl)Cl>[CH2:2]([C@H:5]1[CH2:9][N:8]([C:42]([CH:41]2[CH2:40][C:39]3[C:34](=[CH:35][C:36]([Cl:45])=[CH:37][CH:38]=3)[CH2:33][N:32]2[C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])=[O:43])[CH2:7][C@@:6]1([N:22]=[N+:23]=[N-:24])[C:10]([O:12][CH2:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:11])[CH:3]=[CH2:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67513180HCID 67513180, compoundHCID 131734494HCID 131734494, compound

Product 1

HCID 118216034HCID 118216034, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirred mixture of racemic 2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azidopyrrolidine-3-carboxylate hydrochloride (228 mg, 0.650 mmol) and 2-(tert-butoxycarbonyl)-7-chloro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (258 mg, 0.826 mmol) in methylene chloride (6 mL) was treated with Et3N (0.272 mL, 1.95 mmol) followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU, 321 mg, 0.845 mmol), and the resulting nearly homogeneous mixture was stirred at room temperature. After 1 h, the reaction was diluted with methylene chloride (20 mL), washed successively with water (20 mL), 1 N aqueous HCl (20 mL), saturated aqueous NaHCO3 (20 mL) and saturated aqueous sodium chloride (10 mL), dried over Na2SO4, and concentrated. Purification by silica gel chromatography (40 g column, 15-25% ethyl acetate in hexanes) gave tert-butyl 3-({(3R,4S)-4-allyl-3-azido-3-[(2-oxo-2-phenylethoxy)carbonyl]pyrrolidin-1-yl}carbonyl)-7-chloro-3,4-dihydroisoquinoline-2(1H)-carboxylate (214 mg, 54%) as a pale amber film which was used without further purification. LC-MS ESI+MS found for C31H34ClN5O6 m/z 608.2 (M+H), 630.3 (M+Na); ESI−MS m/z 606.3 (M−H).

Workup

  1. washwashed successively with water (20 mL), 1 N aqueous HCl (20 mL), saturated aqueous NaHCO3 (20 mL) and saturated aqueous sodium chloride (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customPurification by silica gel chromatography (40 g column, 15-25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1fc6c693026a45b3a2ec60eb623fccbf
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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