Diisopropylethylamine → 2-{2-[4-Amino-5-(2-fluoro-4-phenoxy-phenyl)-pyrrolo[2,3-d]pyrimidin-7-ylmethyl]-pyrrolidine-1-carbonyl}-3-cyclopropyl-acrylonitrile

HRID 1529979Notes

Reaction equation

HRID 1529979 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:22]([NH2:24])=[N:21][CH:20]=[N:19][C:18]=2[N:17]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][NH:27]2)[CH:16]=1.[C:31]([C:33](=[CH:37][CH:38]1[CH2:40][CH2:39]1)[C:34](O)=[O:35])#[N:32].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>C(Cl)Cl>[NH2:24][C:22]1[C:23]2[C:15]([C:3]3[CH:4]=[CH:5][C:6]([O:8][C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)=[CH:7][C:2]=3[F:1])=[CH:16][N:17]([CH2:25][CH:26]3[CH2:30][CH2:29][CH2:28][N:27]3[C:34]([C:33](=[CH:37][CH:38]3[CH2:40][CH2:39]3)[C:31]#[N:32])=[O:35])[C:18]=2[N:19]=[CH:20][N:21]=1

Participants

6

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 705130332-Cyano-3-cyclopropylprop-2-enoic acidHCID 867145465-(2-fluoro-4-phenoxy-phenyl)-7-pyrrolidin-2-ylmethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

Product 1

HCID 780792982-{2-[4-Amino-5-(2-fluoro-4-phenoxy-phenyl)-pyrrolo[2,3-d]pyrimidin-7-ylmethyl]-pyrrolidine-1-carbonyl}-3-cyclopropyl-acrylonitrileYield 54.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-(2-fluoro-4-phenoxy-phenyl)-7-pyrrolidin-2-ylmethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (100 mg, 0.25 mmol, 1.0 eq), 2-cyano-3-cyclopropyl-acrylic acid (42 mg, 0.3 mmol, 1.2 eq) and DIEA (97 mg, 0.75 mmol, 3.0 eq) in 10 ml of DCM was added HATU (145 mg, 0.38 mmol, 1.5 eq). The mixture was stirred for 4 h at RT under N2. LCMS showed the reaction was completed. The reaction mixture was concentrated and purified by Pre-TLC to provide 71 mg (54%) of the title compound. LCMS: m/z 523.2 (M+H)+. 1HNMR (400 MHz, DMSO-d6): δ 0.866˜0.920 (m, 2H), 1.177˜1.194 (m, 2H), 1.569 (m, 1H), 1.721 (m, 2H), 1.883 (m, 2H), 3.200 (m, 2H), 3.511 (m, 1H), 4.360˜4.475 (m, 2H), 6.125(m, 2H), 6.642-6.664 (m, 1H), 6.898-6.920 (m, 1H), 6.977-7.010 (m, 1H), 7.150˜7.232 (m, 4H), 7.371-7.471 (m, 3H) and 8.131 (m, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by Pre-TLC

Sources & evidence

ORD record
ord-9f2d9d029a15461bb13a687df5726023
Source dataset
uspto-grants-2015_07
Patent number
US09090621B2

Reaction notes

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