Diisopropylethylamine → HCID 67501872, compound

HRID 513304Notes

Reaction equation

HRID 513304 reaction equation
[F:1][C:2]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=[C:8]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH:7]=1.O.[CH3:34][N:35]1[CH2:42][CH2:41][CH2:40][C@H:36]1[C:37](O)=[O:38].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN1C(=O)CCC1>[F:1][C:2]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=[C:8]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([CH:22]3[CH2:23][CH2:24][N:25]([C:37]([C@@H:36]4[CH2:40][CH2:41][CH2:42][N:35]4[CH3:34])=[O:38])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 162119581-Methyl-L-proline--water (1/1)HCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Product 1

HCID 67501872HCID 67501872, compoundYield 64.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The mixture of compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (50 mg, 0.11 mmol), N-methyl-L-proline monohydrate (33 mg, 0.22 mmol), DIEA (180 μL, 1.1 mmol) in 4 mL NMP was stirred at RT. To it was added BOP (210 mg, 0.55 mmol). The mixture was stirred for overnight, quenched with TFA, and subjected to reverse phase preparative HPLC to isolate the title compound (39 mg). MS found for C30H34F2N6O2 as (M+H)+ 549.5. UV: λ=259 nm. 1H NMR (a pair of rotomers): (CD3OD) δ 8.18 (1H, s), 7.32 (with 7.33, 2H, d, J=8.4 Hz), 7.25 (1H, m), 7.17 (1H, m), 7.13-7.07 (3H, m), 5.77 (with 5.79, 1H, s), 4.68 (2H, m), 4.57 (1H, m), 4.54 (2H, s), 3.90 (1H, m), 3.74 (1H, m), 3.27 (1H, m), 2.93 (with 2.97, 3H, s), 2.90 (2H, m), 2.68 (1H, m), 2.25 (1H, m), 2.11-1.95 (4H, m), 1.82-1.63 (2H, m) ppm.

Workup

  1. stirringThe mixture was stirred for overnight
  2. customquenched with TFA

Sources & evidence

ORD record
ord-8c455a47bcf745acb920d575ea1c5290
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

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