Diisopropylethylamine → HCID 69026060, compound

HRID 1272388Notes

Reaction equation

HRID 1272388 reaction equation
[CH3:1][C:2]([CH3:29])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:9][C:10](O)=[O:11])=[O:6])[CH3:3].Cl.[F:31][C:32]([F:44])([F:43])[C:33]1[N:34]=[CH:35][C:36]2[CH2:42][CH2:41][NH:40][CH2:39][C:37]=2[N:38]=1.C(N(C(C)C)CC)(C)C.ON1C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C>[CH3:1][C:2]([CH3:29])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[O:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:9][C:10]([N:40]1[CH2:41][CH2:42][C:36]2[CH:35]=[N:34][C:33]([C:32]([F:44])([F:31])[F:43])=[N:38][C:37]=2[CH2:39]1)=[O:11])=[O:6])[CH3:3]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18456518HCID 18456518, compoundHCID 69029554HCID 69029554, compound

Product 1

HCID 69026060HCID 69026060, compoundYield 86.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 363 mg (0.9 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]4-(2-benzyloxy-5-fluorophenyl)butanoic acid, 72 mg (0.3 mmol) of 2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride, 0.174 mL (1.0 mmol) of diisopropylethylamine, 136 mg (1.0 mmol) of 1-hydroxy-7-azabenzotriazole (HOAT) and 380 mg (1.0 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) in 5 mL of dichloromethane was stirred under an atmosphere of nitrogen overnight. The reaction mixture was diluted with 100 mL of ethyl acetate, washed sequentially with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine, dried over magnesium sulfate, and concentrated. Purification by preparative TLC (silica gel, 70% ethyl acetate/hexane) gave 152 mg (86%) of the title compound.

Workup

  1. washwashed sequentially with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customPurification by preparative TLC (silica gel, 70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b1e8612a50f04f66bdd6702d8ecc9101
Source dataset
uspto-grants-2007_04
Patent number
US07208498B2

Reaction notes

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