Triethylamine → US9611269, Example 42

HRID 2363360Notes

Reaction equation

HRID 2363360 reaction equation
[C:1]([CH2:3][C:4]1([N:17]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]4[NH:28][CH:29]=[CH:30][C:23]=34)[CH:19]=[N:18]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14](O)=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2].Cl.[CH:32]1([C@H:35]([NH2:40])[C:36]([F:39])([F:38])[F:37])[CH2:34][CH2:33]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.CO>[C:1]([CH2:3][C:4]1([N:17]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]4[NH:28][CH:29]=[CH:30][C:23]=34)[CH:19]=[N:18]2)[CH2:5][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([NH:40][C@@H:35]([CH:32]3[CH2:34][CH2:33]3)[C:36]([F:39])([F:38])[F:37])=[O:15])=[N:12][CH:13]=2)[CH2:7]1)#[N:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 56595197(1S)-1-cyclopropyl-2,2,2-trifluoroethan-1-amine hydrochlorideHCID 711436465-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylic acid

Product 1

HCID 71155854US9611269, Example 42Yield 27.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylic acid (10 mg, 0.02 mmol), (1S)-1-cyclopropyl-2,2,2-trifluoroethanamine HCl salt (6.6 mg, 0.037 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (12 mg, 0.027 mmol) and triethylamine (16 μL, 0.11 mmol) in N,N-dimethylformamide (0.3 mL) was stirred at room temperature for 3 h. It was diluted with methanol, purified by RP-HPLC (pH=2) to afford the desired product (2.9 mg) as TFA salt. LCMS (M+H)+: m/z=522.4. 1H NMR (500 MHz, DMSO-d6): δ 12.01 (s, 1H), 8.92 (s, 1H), 8.90 (d, J=9.4 Hz, 1H), 8.69 (d, J=1.1 Hz, 1H), 8.41 (s, 1H), 8.27 (d, J=5.3 Hz, 1H), 8.04 (d, J=1.0 Hz, 1H), 7.65-7.57 (m, 1H), 7.46 (d, J=5.3 Hz, 1H), 7.01 (s, 1H), 4.84 (d, J=9.8 Hz, 2H), 4.58 (d, J=9.8 Hz, 2H), 4.10-3.97 (m, 1H), 3.78 (s, 2H), 1.46-1.33 (m, 1H), 0.73-0.61 (m, 1H), 0.61-0.53 (m, 1H), 0.53-0.44 (m, 1H), 0.27-0.17 (m, 1H),

Workup

  1. custompurified by RP-HPLC (pH=2)

Sources & evidence

ORD record
ord-2d5f6bce9808451e9f7aafae38cc3e9c
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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